Newsletter Issue 33

December 22, 2014

EDITORIAL 50 years SAKK – 50 years of progress

T

he history of SAKK – our national clinical cancer research network – is a success story. No reason to sit back and relax! Three important factors determine our future. For a start, the Swiss public health system is rapidly changing – and so is SAKK. Secondly, medical and pharmacological progress and their consequences have forced our organization to constantly adapt and develop in order to meet the demands of patients and physicians. Thirdly, current changes in our research environment request major adjustments in the organization of SAKK. Nothing new indeed, during the 50 years of SAKK’s history, the only constant has been change. But the vision of SAKK persists: we want to bring progress to cancer care! At present, major developments affect the performance of SAKK. New instruments in the development of anticancer drugs and tests, genetic testing of tumors, functional imaging, germ-line testing and many more, request specific coping strategies. All these improvements in biotechnology and eventually in cancer medicine offer a chance for major progress in treatment and patient outcome but are also a major challenge for SAKK. The new law on research in humans together with the upcoming new EU directive created, and may further create, major obstacles. All these developments will need adaption of our operating procedures and regulations. In addition, costs become an increasingly important factor in the Public Health System and in particular in the financing of academic clinical trials. In order to meet financial challenges, SAKK is constantly working on new financing models and increasing the third party funding. SAKK is busy adapting and getting ready for these challenges.

In Brief New ways of collaborations On December 11, representatives of patient organizations, authorities, academic research and the pharmaceutical industry met for a workshop to discuss how the concerns of patients can be better integrated in research. PAGE 3 The General Assembly and the winter semi-annual meeting took place in St.Gallen.  PAGE 6

Contents SAKK News 2-5 Trial News 9-13 Publications, Presentations 14 IBCSG15-17 ETOP17+18 Cancer League 19+20 Various, Education, Events 21-24 Dates, Flag 25

So let us take advantage of the 50th anniversary of SAKK to create the best possible conditions for our future. The countdown is running – only 10 days to the official beginning of the festivities. Preparations are being finalized, sponsors and ambassadors acquired and everyone in the network is called to take part in spreading SAKK’s vision throughout Switzerland. Planned national events: May 20, 2015 June 2015 October 2015 November 2015

Public event and press conference on the international clinical trials’ day Plenary lecture at the semi-annual meeting in Zurich Scientific Symposium with DGHO in Basel Symposium at the semi-annual meeting in Zurich

You will find all information and material for the anniversary on www.sakk.ch in January 2015. Join us to bring progress to the next 50 years of SAKK! Prof. Dr. Beat Thürlimann, SAKK President

The Swiss Oncology Research Network

2  December 22, 2014

SAKK Newsletter

SAKK NEWS Board decisions At its board meeting on October 21, 2014, in Bern, the SAKK board accepted to participate in the following international trials: IELSG-43, G. Illerhaus, T. Pabst High-dose chemotherapy and autologous stem cell transplant consolidating conventional chemotherapy in primary CNS lymphoma -randomized phase III trial. IELSG-42, A. Ferreri, P. Samaras An international phase II trial assessing tolerability and efficacy of sequential Methotrexate-Aracytin-based combination and R-ICE combination followed by high-dose chemotherapy supported by autologous stem cell transplant in patients with systemic DLBCL with CNS involvement at diagnosis or relapse (MARIETTA regimen).

Awards and Promotions Grant for Oncology Innovation 2014 Ulrich Güller and Markus Jörger from the Department

of Oncology & Haematology at the Cantonal Hospital St.Gallen have received the Merck Serono award “Grant for Oncology Innovation (GOI) 2014”. They received the research award for the trial SAKK 41/13 “Prospective double-blinded, placebo-controlled, randomized trial of adjuvant aspirin treatment in PIK3CA mutated colon cancer patients”, U. Güller & M. Jörger

which is being conducted at centres of the SAKK network. The project, which was selected from 143 applications submitted from 25 different countries, is now receiving support to the tune of 300,000 euros. The Grant for Oncology Innovation, which was awarded at the annual congress of the European Society of Medical Oncology (ESMO) in Madrid, is designed to promote high-quality scientific projects that explore new therapeutic strategies for individualized oncological treatment. President of the project group Urogenital Tumors, Richard Cathomas, was appointed to Deputy Head Physician at the Oncology/Hematology department of the Cantonal Hospital in Chur.

The Swiss Oncology Research Network

Member of the SAKK network, Niklaus Schaefer, was nominated as Professor at the Faculty of Medicine of Zurich. He is a trained medical oncologist, internist and nuclear physician.

SAKK CC Staff News Celebrations

N. Schäfer

In October, Silvia Hanselmann Moser celebrated her 25-year jubilee at the SAKK Coordinating center. She started in 1989 to work as trial coordinator (named “data manager” at that time) on the trial SAKK 08/88 in a team constituted of 2 data managers, 1 statistician, 1 IT specialist and a part time director. Over the years, she has lived the 25-year jubilee of the SAKK, the development of the SAKK CC and its move to its actual location. She has contributed herself as well to these developments taking over additional responsibilities as Flying Data Manager in 1993 and as monitor in 2004. Her year-long experience at the SAKK CC and at the Hospital of Biel as CRC is an asset for our Monitoring team and the SAKK CC. We thank her for her great S. Hanselmann contribution over the past years and wish her all the best for the coming ones. We are looking forward to continue our collaboration with her. Karin Rothgiesser Franco celebrates her five-year-jubilee

at the SAKK CC in January 2015. We thank her for her great work and commitment! With her five-year-jubilee at the SAKK CC, Simona Berardi Vilei has been promoted to Innovation and Business Development Manager. Her main responsibilities will be the acquirement of new phase I trials. In this position, she reports directly to the CEO. Simona will take over this new function with 30 % part time in January 2015. For the time being, she will keep her responsibilities as Head of Clinical Project Management in the team of Christoph Kolb with a 70 % work load. We wish her thrilling experiences and many successes, so that new treatments can be brought forward to the benefit of patients.

SAKK Newsletter

December 22, 2014  3

SAKK NEWS Farewell Robert Meyer, Head of Services, will leave the SAKK CC.

We thank him for his commitment and dedication to SAKK and we wish Robert all the best for his future. For information on job vacancies at SAKK, please contact us and/or refer to http://sakk.ch/en/about-sakk/organization/jobs/

2nd Orphan Malignancies Seminar On September 18, a multidisciplinary faculty of Swiss experts including surgeons, radiation oncologists, pathologists and oncologists gathered in Zürich to discuss the management of patients with thymic neoplasms and the optimal treatment of small cell lung cancer. The seminar was moderated by Frank Stenner from the University Hospital Basel and Richard Cathomas from the Kantonsspital Graubünden. The Orphan Malignancies Seminar has been created to discuss rare malignant diseases as well as neoplasias that are not covered in depth at the various annual conferences. It aims to bring Swiss experts in the respective diseases together and facilitate interdisciplinary collaboration. Rare diseases are defined according to incidence (< 5 people in 100'000 affected) or according to prevalence (1 in 5000 people affected). Approximately 20 % of all cancers are rare cancers according to this definition and over 180 different rare cancers have been defined. The outcome for patients affected of rare cancers is inferior as compared to common cancers, especially in elderly patients. The SAKK has taken over the patronage of the Orphan Malignancies Seminar in 2014. GlaxoSmithKline AG was the main sponsor of the event, AstraZeneca AG, Merck (Schweiz) AG, Novartis Pharma AG and Takeda Pharma AG have also provided funding. It is planned to continue the seminar on a yearly basis with oncological and hematological topics. The seminar series is intended to promote interdisciplinary networking for rare cancers in Switzerland and should give an interested audience the possibility to exchange knowledge with national experts and to build new partnerships. The next seminar will take place on September 18, 2015, in Zurich. See announcement on page 22 for details.

Research should be informed by experiences and needs of patients On December 11, representatives of patient organizations, authorities, academic research and the pharmaceutical industry met in Bern for a workshop to discuss how the concerns of patients can be better integrated in research. Many patients affected by chronic or serious diseases, along with their families, would like to see their experiences and needs being taken into account in their treatment, in the development of medicines and also to be more actively involved in clinical research. At the same time, it is also a concern of academic research, the pharmaceutical industry and authorities that patients should be better integrated. This has led to various initiatives in recent times, including the establishment of the European platform EUPATI (European Patients Academy on Therapeutic Innovation). This body aims to increase the knowledge of patients and patient organizations, so that they become effective patient representatives and advisors in medical research, for example in the field of clinical trials, with authorities or in ethics committees. Patients should receive scientifically grounded, objective and comprehensible information about research and drug development. The aim of the conference in Bern was to bring together interested organizations from Switzerland and to create the conditions for the establishment of a national organization in the framework of the EUPATI platform. Efforts are being made in Switzerland to improve the involvement of patients but many initiatives are still in their infancy and there is no long history of experience to draw on – interestingly this also applies to companies from the pharmaceutical industry. While new Human Research Act mentions the involvement of patient representatives in ethics committees, this has not been implemented in the law by a single canton. However, patient representatives in the meantime have achieved representation in some cantons on the initiative of the committees. One reason for so many initiatives being in their infancy is certainly that the right contact partners have to be found. The homogeneity of the patient organizations and representatives in Switzerland is still very high. The Swiss Agency for Therapeutic Products (Swissmedic) has established a working group for the integration of patients with representatives of patient and consumer organizations as a two-year pilot project.

The Swiss Oncology Research Network

4  December 22, 2014

SAKK Newsletter

SAKK NEWS The Swiss Cancer League has tried various strategies to involve patients in strategic functions, but it has not been completely successful and is now focused on involving project-related patient organizations. SAKK is also pursuing the strategy of integrating patients more in their future research projects. The idea is that these patients should be able to bring their knowledge to bear in the three pillars of research strategy, study development and communication. In an initial phase, which will start at the beginning of 2015, SAKK aims to select a consortium of patients and develop a set of specifications together with them. Please contact for further information: Dr. Claudia Weiss, Politics & Development, [email protected] Annik Steiner, Communications Manager

[email protected]

New president and members for the Network Outcomes Research The Network Outcomes Research (NOR) under the presidency of Bernhard Pestalozzi and responsible senior researcher Klazien Matter-Walstra (ECPM, University Basel), is active for 7 years. This has been a very productive time for the NOR with the following achievements: in the field of health economic analyses, several literature based studies which found highly international attention (up to 37 citations) and health economic analyses alongside SAKK trials were performed (and of the latter many more are still ongoing or newly activated). In addition, a large study on delivery of care at the end-of-life of Swiss cancer patients has been completed. Furthermore, some methodological topics were covered and general outcomes research and health services research topics were addressed.

Phase I centers: site selection process The conduct of phase I trials – especially of trials with new medication or treatments – so called “first in human trials (FIH)”, require additional and specific preventive measures in order to protect the treated patients. One of these measures includes conducting such trials only at sites with adequately experienced researchers, organization and infrastructure. In order to fulfil this requirement, the SAKK board agreed to implement a risk based site selection auditing process for sites which are interested to conduct such trials. B. Pestalozzi, K. Matter-Walstra, M. Schwenkglenks

End of 2013, this program was accepted by the General Assembly and implemented since January 2014. Up to now, the following sites were approved by SAKK for FIHtrials: • Cantonal Hospital St.Gallen • IOSI Ticino • Cantonal Hospital Chur • University Hospital Geneva • University Hospital Bern Further sites are in the evaluation process. All approved sites are re-assessed by routine site selection audits within 2-3 years to ensure sufficient long term quality. Dr. Peter Durrer Head of Quality Assurance & Regulatory Affairs

[email protected]

The Swiss Oncology Research Network

As Bernhard Pestalozzi has been elected as member of the SAKK board in 2013, he needs to step down as president of the network in the coming future. So far, Bernhard supported the Network enormously – with his encouragement, the network has gained visibility within the SAKK community and beyond. This has resulted in an increasing number of requests to assist/co-operate in interesting cancer related outcomes research projects. When it is time to bid farewell to Bernhard we will do so with much regret but with the knowledge to have his further support within the SAKK. We already now thank Bernhard Pestalozzi for all his great work and wish him best of luck for his term as SAKK board member. Potential candidates for the vacant presidency of the network are now being searched for. Persons with a good contact to daily clinical practice, interest in health services

December 22, 2014  5

SAKK Newsletter

SAKK NEWS and outcomes research, including health economics, and willing to actively shape the work of the network are welcomed to convey their interest. The exact time point for the election of the new president still has to be defined, but we expect it to be in the coming year. You may directly contact Peter Brauchli if you would like to stand for presidency. For further Information please contact Klazien Matter-Walstra or Bernhard Pestalozzi. Additionally, other interested members of the SAKK network are highly welcome joining the network as the development of new research projects, especially in the field of Health Services Research, would need the contribution of new members.

due to the following reasons: 1. Time to first bone metastasis is not a meaningful endpoint 2. No influence on overall survival 3. No improvement in pain or quality of life 4. ONJ correlates with the duration of therapy

Dr. Klazien Matter-Walstra, Senior Researcher NOR

Dr. Arnoud Templeton, [email protected] PD Dr. Roger von Moos, [email protected]

[email protected]

Denosumab (Xgeva®) for men with bone metastases from castration resistant prostate cancer only! Denosumab (Xgeva®) can delay the occurrence of skeletal events (defined as pathological fracture, radiation therapy, surgery to bone, or spinal cord compression) 1,2. The results of several preclinical and clinical trials suggest that Denosumab given every 12 weeks is non-inferior to Denosumab given every 4 weeks. In order to test this formally, SAKK has developed the multi-center phase III noninferiority trial SAKK 96/12, which is financially supported by santésuisse and open for accrual in most Swiss centres. Women with breast cancer and men with castration resistant prostate cancer are eligible. In men with metastatic prostate cancer, treatment with Denosumab is occasionally started already when the disease is still hormone sensitive. So far, there is no data showing a benefit of a Denosumab treatment in patients with hormone sensitive prostate cancer. Recently, data from a novel trial was published where it was shown that zoledronic acid (e.g. Zometa®), a drug with a similar effect as Denosumab, was not beneficial for patients with hormone sensitive prostate cancer3. Importantly, the side-effects of Denosumab in a long-term treatment are not negligible; especially the incidence of osteonecrosis of the jaw (ONJ) increases significantly with duration of the treatment.

On the basis of this data be believe that the drug label for Xgeva® in Switzerland is imprecise. Denosumab should only be used for treatment of men with bone metastases from castration resistant prostate cancer (ideally within the above-mentioned trial SAKK 96/12).

References 1. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-22. 2. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010;28:5132-9. 3. Smith MR, Halabi S, Ryan CJ et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014 Apr 10;32(11):1143-50. 4. Smith MR, Saad F, Oudard S et al. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol. 2013 Oct 20;31(30):3800-6.

Furthermore, Denosumab should not be used in men with castration resistant prostate cancer without bone metastasis. Although a trial showed an increased time until the occurrence of bone metastases4, Denosumab was neither approved in this indication by the FDA nor by the EMA

The Swiss Oncology Research Network

6  December 22, 2014

SAKK Newsletter

GENERAL ASSEMBLY & SEMI-ANNUAL MEETING Meeting of the SAKK board, group presidents and executive committee of the SAKK CC A total of 40 participants attended this meeting before the General Assembly. After a short review of lessons learnt since the last meeting, the presidents and board members covered several hot topics. The SAKK CC staff gave an overview of the current number of activated trials in 2014 (4 SAKK and 4 foreign trials) and measures to increase trial activation were discussed. Also, inputs for a research strategy were collected as the State Secretariat for Education, Research and Innovation SERI has requested such guidelines of SAKK. These points were mentioned: • Large academic Phase III trials to optimize therapy standards • Clinical trials with a strong translational research component • Clinical trials addressing rare cancer diseases • Clinical trials investigating new drugs It was agreed to establish collaboration with patient organizations to better involve patients’ needs in clinical research and drug development. The start of this project took place at the EUPATI meeting on December 11, 2014 (see page 3 for detailed report). Furthermore, it was emphasized that the collaboration between the different groups should be made more productive by developing transversal SAKK protocols, efficient interaction between all involved parties, good communication and immediate exchange of news. The project group lung cancers suggested the implementation of a “trial radar list” with trials not directly sponsored by SAKK. SAKK will provide a platform in the members’ section of the SAKK website.

General Assembly During the General Assembly, which took place on November 19, 2014, the participants were informed about the political issues and other ongoing processes that will influence the work of SAKK in the coming years. Elections One seat in the Board was available for election: Michele Ghielmini stepped down from his function as a Board member. The election was held with 16 voting members present. Christiana Sessa was unanimously elected – she is representing the Italian speaking part of Switzerland. Sessa is a well-known member of the SAKK network

The Swiss Oncology Research Network

for her long-term commitment and activity in the field of new drug development and gynaecological oncology. She is a worldwide reference person in these two topics and is a common speaker on international congresses. Many thanks go to Michele Ghielmini for his great work in the SAKK board and long term commitment to SAKK.

C. Sessa, M. Ghielmini

Accrual per Swiss center in the annual report The Swiss Cancer League and the Cancer Research Switzerland have suggested including the accrual numbers per center and disease group in the annual report. The member representatives accepted this proposition. Henceforth, the figures will be shown in the annual report. System for referral of patients Simona Berardi, Head Clinical Project Management, presented a system for the referral of patients, the focus lays on phase I trials and rare disease trials. The patient fee is divided between the respective centers according to the conducted work. The referring site will receive one point for each included patient and the treatment site will also receive one point for each treated patient. To stay or become a SAKK voting member, a center needs 20 points per year. The members agreed to the implementation of this project. The next step is the preparation of a detailed concept which will be soon submitted to the SAKK board and afterwards to swissethics.

SAKK Newsletter

December 22, 2014  7

GENERAL ASSEMBLY & SEMI-ANNUAL MEETING Swissmedic inspection in September 2014 The inspectors’ feedback at the close out meeting was positive. The CAPA plan (Corrective and Preventive Action) of the last inspection was implemented as announced and there were no repeated findings. Swissmedic’s confidence in SAKK increased due to this inspection. Nevertheless, some findings were addressed by the investigators – after the reception of the official report, SAKK will submit a respective CAPA plan. Audit by the Swiss National Fonds SNF The audit generated a rather high workload for the SAKK CC, the president as well as selected board members and a hearing took place. The reception of the final report of the SNF is expected soon.

GIST-Award The GIST Group Switzerland has awarded its science prize for the fifth time. The honor goes to Anette Duensing, M.D., Assistant Professor of Pathology, currently at the University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. The laudatory speech was given by SAKK vice-president Roger von Moos and Member of the GIST Group Award Committee. The prize endowed with CHF 10,000 was awarded for the study “Unbiased Compound Screening Identifies Unexpected Drug Sensitivities and Novel Treatment Options for Gastrointestinal Stromal Tumors”, published in Cancer Research 2014.

Most gastrointestinal stromal tumors (GIST) can be successfully treated with the targeted therapy drug imatinib

Semi-Annual Meeting SAKK held its winter semi-annual meeting on November 20 and 21, 2014, at the Congress Hotel Einstein in St.Gallen. In addition to the sessions within the various SAKK research groups, the GIST award and the Candy Heberlein research prize were granted. The semiannual meeting provided once again an excellent platform to network and to foster the personal dialogue between experts, health professionals and other interested people in the field of cancer research. It was a pleasure to welcome such a remarkable number of participants and to assist in high-quality discussions. Many highlights were discussed within the various SAKK working and project groups and at the meetings of our partner organizations, connecting their expertise in joint meetings. We look forward to meeting you again on June 25 and 26, 2015 in Zurich at our next SAKK Semi-Annual Meeting – please save the date.

Research Grants

Excited Audience at the Award ceremony

Preparations for the laudatio, from left to right: U. Schanz, B. Thürlimann, R. von Moos

mesylate (Glivec®/Gleevec®). However, approximately 50 % of patients experience resistance to the drug within the first two years of treatment after initially benefiting from the therapy. Although second- and third-line regimens are available, they often only offer limited success. Therefore, new therapeutic strategies are urgently needed. In the study, Anette Duensing’s team performed a highthroughput drug screening to identify new treatment options for GIST patients. The panel included 89 drugs that are already approved for cancer treatment by the U.S. Food and Drug Administration (FDA). The experiments successfully identified two major drug classes as being very effective in destroying GIST cells – even those that are resistant to Glivec. This was unexpected, because most of the drugs included in the collection were “classical” chemotherapeutic agents – drugs that are traditionally known as not being effective in GIST. However, the above notion comes from studies that had been conducted before a reliable diagnosis of GIST was possible (i.e., before 1999). Hence, a number of non-GIST malignancies may

The Swiss Oncology Research Network

8  December 22, 2014

SAKK Newsletter

SEMI-ANNUAL MEETING have inadvertently been included. Moreover, a systematic testing of chemotherapeutic agents in GIST has not been done, in part due to the rarity of the disease.

the transplanted patient displaying a highly compromised immune defence system and thus extreme susceptibility to infections, especially virus infections.

In summary, by applying the high-throughput screening study the researchers were able to successfully identify two classes of FDA-approved cancer drugs that are highly effective in GIST cell lines and GIST in vivo models. Clinical trials to test these drugs in GIST patients are currently being initiated.

The SFK President Candy Heberlein has often been confronted with this particular issue in her SOS patient groups. She hopes to be able to offer patients better post-transplantation support in the future. The laudatory speech was given by PD Dr. med. Urs Schanz, consultant at the Zurich University Hospital and an expert in stem cell transplantation. The SFK wants to make it easier for patients who need a bone marrow transplantation for their condition to have access to this treatment option. It informs patients and the public about the limits, possibilities and technical aspects of bone marrow transplantation and is constantly attracting new, voluntary donors of blood stem cells. Further information on the SFK and its activities can be found at: www.knochenmark.ch

Zurich researcher receives the Candy Heberlein research prize

H. Meier from The GIST Group Switzerland with award winner A. Duensing and SAKK vice-president R. von Moos

The SFK (Swiss Foundation for the Promotion of Bone Marrow Transplantation) awarded the Candy Heberlein research prize for the first time at the SAKK semi-annual meeting on 20 November. The award went to Dr. med. Antonia Müller from Zurich University Hospital. Antonia Müller received the prize, which is worth of 30,000 francs, for her work on the “Complex interactions after blood stem cell transplantation – immune function, pharmacological immunosuppression, GVHD and CMV reactivation”.

The aim of this project is to study the associations between graft-versus-host disease (GVHD), its drug treatment and the immune function after blood stem cell transplantation. GVHD occurs because the transplanted immune system of the donor identifies the tissue in the recipient as foreign and attacks it. This often severe clinical picture is prevented or treated using medicines that suppress the immune system. On the whole, this leads to

The Swiss Oncology Research Network

C. Heberlein from the SFK with award winner A. Mueller and U. Schanz

SAKK Newsletter

December 22, 2014  9

TRIAL NEWS Trials to be activated 2015, effective December 1, 2014 Trial

Trial Name

Opening of the first site

SAKK 23/13

Randomized Controlled Trial to Evaluate the Impact of a Surgical Sealing Patch on Lymphatic Q1 2015 Drainage after Axillary Lymph Node Dissection for Breast Cancer

Alliance/ Prospect trial

A phase II/III trial of neoadjuvant folfox, with selective use of combined modality chemora- Q1 2015* diation vs. preoperative combined modality chemoradiation for locally advanced rectal cancer patients undergoing low anterior resection with total mesorectal excision

ETOP SPLENDOUR

Survival improvement in lung cancer induced by denosumab therapy. Q1 2015* A randomized phase III trial evaluating the addition of deno-sumab to standard first-line anticancer treatment in ad-vanced NSCLC

LungArt (IFCT-EORTC)

Phase III study comparing post-operative conformal radiotherapy to no post-operative ra- Q1 2015* diotherapy in patients with completely resected non-small cell lung cancer and mediastinal N2 Involvement

BIG 6-13

A randomised, double‐blind, parallel group, placebocontrolled multi‐centre Phase III study to Q1 2015* assess the efficacy and safety of olaparib vs placebo as adjuvant treatment in patients with high risk germline BRCA mutated HER2‐negative breast cancer who have completed definitive local and systemic neoadjuvant/adjuvant treatment

SAKK 06/14

A phase I/II open label clinical trial assessing safety and efficacy of intravesical instillation Exp. Q1-2 2015 of the recombinant BCG VPM1002 in patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy

SAKK 25/14

Eribulin 1st line in elderly (≥70years) and old patients (>80y) with metastatic breast cancer: Q2 2015 a phase II trial

SAKK 33/14

Effects of sympathicomimetic agonists on the disease course and mutant allele burden in Q2 2015 patients with Jak2-mutatated myeloproliferative neoplasms. A multicenter phase II trial

HOVON 132

Randomized study with a run-in dose-selection phase to assess the added value of lenalido- Q2 2015* mide in combination with standard remission-induction chemotherapy and post-remission treatment in patients aged 18-65 years with previously untreated acute myeloid leukemia (AML) or high risk myelodysplasia (MDS) (according to IPSS-R risk score > 4.5)

SAKK 36/13

Combination of Ibrutinib and Bortezomib to treat mantle cell lymphomas patients – a mul- Exp. Q2-3 2015 ticenter phase I/II trial

SAKK 41/13

Adjuvant aspirin treatment in PIK3CA mutated colon cancer patients. A randomized, double- Q3 2015 blinded, placebo-controlled, phase III trial

GRAALL-2014

Treatment of adult acute lymphoblastic leukemia (ALL), evaluating the addition of a second Q3 2015* late intensification course in B-lineage PH-negative ALL, the addition of Nelarabine in highrisk T-lineage ALL, and the reduction of chemotherapy intensity in Ph+ ALL

IELSG-43

High-dose chemotherapy and autologous stem cell transplant consolidating conventional Exp. Q3 2015* chemotherapy in primary CNS lymphoma -randomized phase III trial

IELSG-42

An international phase II trial assessing tolerability and efficacy of sequential Methotrexate- Exp. Q3 2015* Aracytin-based combination and R-ICE combination followed by high-dose chemotherapy supported by autologous stem cell transplant in patients with systemic DLBCL with CNS involvement at diagnosis or relapse (MARIETTA regimen)

*Dependent on the cooperative group, just an estimated opening for accrual

The Swiss Oncology Research Network

10  December 22, 2014

SAKK Newsletter

Trials to be activated 2015, effective December 1, 2014 Trial

Trial Name

Opening of the first site

SAKK 35/14

Extended Rituximab with or without Ibrutinib. A randomized blinded Phase II trial

Q3-4 2015

TRIANGLE

Efficacy of Ibrutinib during R-CHOP/R-DHAP induction and after or in comparison to autolo- Exp. Q3-4 2015* gous stem cell trasnaplantation (ASCT) in previously untreated patients with mantle cell lymphoma

SAKK 08/14

Enzalutamide in combination with metformin vs. enzalutamide in patients with CRPC pro- Exp. Q3-4 2015 gressing on androgen deprivation therapy (ADT)

SAKK 06/13

BOOST: A prospective placebo controlled randomized study comparing intradermal BCG im- Exp. Q4 2015 munization before intravesical BCG to standard intravesical BCG therapy alone in patients with non-muscle invasive bladder cancer

Trials Open for Accrual December 2014 Disease Group

Trial Name

Trial Description

Urogenital Cancers

SAKK 01/10

Urogenital Cancers

Accrual Target

Current Estimated Accrual* Closure for Accrual

Trial Coordinator

Involved Node Radiotherapy and Carboplatin 115 Chemotherapy in Stage IIA/B Seminoma

26

[email protected]

SAKK 63/12

Prospective cohort study with collection of 1930 clinical data and serum of patients with prostate disease

13

Urogenital & Breast Cancers

SAKK 96/12

Prevention of Symptomatic Skeletal Events 1380 with Denosumab Administered every 4 Weeks versus every 12 Weeks – A Non-Inferiority Phase III Trial

35

31.12.2017

lukas.stalder@ sakk.ch

Urogenital Cancers

STAMPEDE Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy A 5-stage multi-arm randomised controlled trial

46

31.12.2016

estelle.cassoly @sakk.ch

Lung Cancers

SAKK 15/12

Early prophylactic cranial irradiation with hip- 42 pocampal avoidance in patients with limited disease small-cell lung cancer. A multicenter phase II trial

4

11.05.2016

andrea.fuhrer@ sakk.ch

Lung Cancers

SAKK 16/08

Preoperative chemotherapy and radiotherapy 69 with concomitant Cetuximab in non-small cell lung cancer (NSCLC) patients with IIIB disease. A multicenter phase II trial

52

30.12.2015

vincent.bize @sakk.ch

Breast Cancers

SAKK 21/12

A Phase I and stratified, multicenter Phase II 105 trial of transdermal CR1447 (4-OH-testosterone) in endocrine responsive-HER2 negative and triple negative-androgen receptor positive metastatic or locally advanced breast cancer

8

31.12.2016

karin.rothgiesser@ sakk.ch

Breast Cancers

EORTC EORTC 10085 prospective part, Clinical and biological 10085 PRO characterization of Male Breast Cancer: an international EORTC, BIG and NABCG intergroup study

10

30.06.2016

estelle.cassoly@ sakk.ch

15.06.2017

vincent.bize@sakk. ch

*Current accrual as of end of November, 2014. Accrual for non-SAKK trials only includes patients enrolled at SAKK centers.

The Swiss Oncology Research Network

December 22, 2014  11

SAKK Newsletter

TRIAL NEWS Trials Open for Accrual December 2014 Disease Group

Trial Name

Trial Description

Breast Cancers

SAKK 22/10

Current Estimated Accrual* Closure for Accrual

Trial Coordinator

A randomized phase II trial of pertuzumab in 208 combination with trastuzumab with or without chemotherapy, both followed by T-DM1 in case of progression, in patients with HER2positive metastatic breast cancer

98

30.11.2015

marie-aline. [email protected]

Breast Cancers

IBCSG 42-12 A randomized phase II study evaluating differ- 240 SNAP ent schedules of nab-Paclitaxel in metastatic breast cancer

51

Q4 2015

ibcsg42_SNAP @fstrf.org

Breast Cancers

IBCSG 43-09 Prospective observational study of young 300 HOHO women (£ 40 years at diagnosis) with breast cancer. Data analyzed will include serial patient surveys and medical record information

60

Q4 2015

Monica.Ruggeri @ibcsg.org

Breast Cancers

IBCSG 4814/BIG 8-13

A study evaluating the pregnancy outcomes 500 and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy

1

Leukemias

APL 2006

Randomized phase III trial assessing the role 800 of arsenic trioxide and/or ATRA during consolidation course in newly diagnosed acute promyelocytic leukemia (APL)

59

15.05.2016

fatma.karabulut @sakk.ch

Leukemias

CML V

Treatment optimization of newly diagnosed 628 Ph/BCR-ABL positive patients with chronic myeloid leukemia (CML) in chronic phase with nilotinib vs. nilotinib plus interferon alpha induction and nilotinib or interferon alpha maintenance therapy

4

23.08.2015

[email protected]

Leukemias

EBMT HCT vs CT

Compare conventinal chemotherapy to low 231 dose total body irradiation-based conditioning and hematopoietic cell transplantation as consolidation therapy

7

31.12.2015

fatma.karabulut @sakk.ch

Lymphomas SAKK 39/10

Nelfinavir and lenalidomide/dexamethasone 35 in patients with progressive multiple myeloma that have failed lenalidomide-containing therapy. A single arm phase I/II trial

9

31.03.2016

michael.beyeler @sakk.ch

Lymphomas SAKK 39/13

Nelfinavir and lenalidomide/dexamethasone 34 in patients with progressive multiple myeloma that have failed lenalidomide-containing therapy. A single arm phase I/II trial

0

31.08.2016

catherine.berset@ sakk.ch

Lymphomas HD 16

HD16 for early stages: Treatment optimization trial in the first-line treatment of early stage Hodgkin lymphoma; treatment stratification by means of FDG-PET

51

30.09.2015

katrin.eckhardt @sakk.ch

Updated

Accrual Target

Monica.Ruggeri @ibcsg.org

*Current accrual as of end of November 2014. Accrual for non-SAKK trials only includes patients enrolled at SAKK centers.

The Swiss Oncology Research Network

12  December 22, 2014

SAKK Newsletter

TRIAL NEWS Trials Open for Accrual December 2014 Lymphomas HD 17

Therapieoptimierungsstudie in der Primärther- 1100 apie des intermediären Hodgkin Lymphoms: Therapiestratifizierung mittels FDG-PET

39

01.12.2016

katrin.eckhardt @sakk.ch

Lymphomas REMoDL-B

A randomised evaluation of Molecular guided 940 therapy for Diffuse Large B-Cell Lymphoma with Bortezomib (phase III)

65

30.06.2015

[email protected]

Lymphomas IELSG-37

A randomized, open-label, multicentre, two- 376 arm phase III comparative study assessing the role of involved mediastinal radiotherapy after Rituximab containing chemotherapy regimens to patients with newly diagnosed Primary Mediastinal Large B-Cell Lymphoma (PMLBCL)

5

31.12.2016

simona.berardi @sakk.ch

Lymphomas T-cell project Das T-Cell project ist eine Registrierstudie mit Referenzpathologie um Daten zu seltenen malignen Erkrankungen der T-Zell Linie zu gewinnen

29

31.01.2015

simona.berardi @sakk.ch

Gastrointestinal Cancers

SAKK 41/10

Cetuximab monotherapy versus cetuximab plus 78 capecitabine as first-line treatment in elderly patients with KRAS- and BRAF wild-type metastatic colorectal cancer. A multicenter phase II trial

21

30.01.2015

daniela.baertschi @sakk.ch

New Drugs

SAKK 65/12

Phase I study of LDE225 in combination with 22 Paclitaxel in patients with advanced solid tumors

13

15.06.2015

milica.enoiu @sakk.ch

New Drugs

SAKK 66/12

A Phase I, open-label, multi-center, dose escalation study of oral CGM097, a p53/HDM2-interaction inhibitor, in adult patients with se-lected advanced solid tumors characterized by wildtype TP53

2

30.06.2016

simona.berardi @sakk.ch

New Drugs

SAKK 66/13

INC280 Combination with BKM120 for glio- 58 blastoma patients, Phase I/II trial

1

31.01.2015

simona.berardi @sakk.ch

New Drugs

SAKK 67/13

Phase I study of oral PQR309 in Patients with 70 Advanced Solid Tumors

15

30.06.2015

vincent.bize @sakk.ch

New Drugs

SAKK 69/13

Phase IB of oral BGJ398 (pan FGFR inhibitor) and oral BYL719 (a specific PI3K inhibitor) in adult patients with selected solid tumors

0

30.04.2016

simona.berardi @sakk.ch

Gynaecological Cancers

Mito/ Mango 16b

A multicenter phase III randomized study with 400 second line chemotherapy plus or minus bevacizumab in patients with platinum sensitive epithelial ovarian cancer recurrence after a bevacizumab/chemotherapy first line

4

31.12.2015

[email protected]

Gynaecological Cancers

INOVATYON

Phase III international, randomized study of trabect- 588 edin plus Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin plus PLD in patients with ovarian cancer progressing within 6-12 months of last platinum

10

30.06.2017

[email protected]

Updated *Current accrual as of end of November, 2014. Accrual for non-SAKK trials only includes patients enrolled at SAKK centers.

The Swiss Oncology Research Network

December 22, 2014  13

SAKK Newsletter

TRIAL NEWS (effective December 5, 2014)

Activated trials Urogenital Cancers SAKK 63/12

Prospective cohort study with collection of clinical data and serum of patients with prosate disease

Activated Coordinating investigator Clinical project manager

October 15, 2014 Daniel Engeler, St.Gallen [email protected]

Breast Cancers IBCSG 48-14 A study evaluating the pregnancy outcomes and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy Coordinating investigator Monica Ruggeri Clinical project manager [email protected]

Leukemias Hovon 103 Tosedostat

Activated Coordinating investigator Clinical project manager

A randomized phase II multicenter study with a safety run-in to assess the tolerability and efficacy of the addition of oral tosedostat to standard induction chemotherapy in AML and high risk myelodysplasia (MDS) (IPSS-R > 4.5) in patients aged ≥ 66

November 12, 2014 Georg Stüssi, Bellinzona

[email protected]

Lymphomas SAKK 39/13

Nelfinavir as Bortezomib-sensitizing drug in patients with proteasome inhibitor nonresponsive myeloma

Activated Coordinating investigator Clinical project manager

December 2, 2014 Christoph Driessen, St.Gallen

[email protected]

Trials closed for accrual Lung Cancers BELIEF A phase II trial of erlotinib and bevacizumab in patients with advanced non-small cell

lung cancer and activating EGFR mutations. Bevacizumab and ErLotinib In EGFR mut +

Closed October 9, 2014 Coordinating investigator Oliver Gautschi, Luzern Clinical project manager [email protected] |www| All information on SAKK trials can also be found under www.sakk.ch in the members’ section.

The Swiss Oncology Research Network

14  December 22, 2014

SAKK Newsletter

PUBLICATIONS & PRESENTATIONS Q4 2014 Publications

Outcomes research

Urogenital Cancers

SAKK 89/09 Matter-Walstra KW, Achermann R, Rapold R, Klingbiel D, Bordoni A, Dehler S, Jundt G, Konzelmann I, Clough-Gorr K, Szucs T, Pestalozzi BC, Schwenkglenks M. Cancer-Related Therapies at the End of Life in Hospitalized Cancer Patients from Four Swiss Cantons: SAKK 89/09. Oncology. 2014 Sep 26.

STAMPEDE James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF, McLaren D, Parker CC, Parmar MK, Ritchie AW2, Russell JM, Strebel RT, Thalmann GN, Mason MD, Sydes MR. Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). Eur Urol. 2014 Oct 6. Lung Cancers SAKK 17/04 Rusch A, Ziltener G, Nackaerts K, Weder W, Stahel RA, Felley-Bosco E. Prevalence of BRCA-1 associated protein 1 germline mutation in sporadic malignant pleural mesothelioma cases. Lung Cancer. 2014 Nov 6. Gastrointestinal Cancers SAKK 60/00 Klingbiel D, Saridaki Z, Roth AD, Bosman F, Delorenzi M, Tejpar S. Prognosis of stage II and III colon carcinoma treated with adjuvant 5-FU or FOLFIRI in relation to microsatellite status, results of the PETACC-3 trial. Ann Oncol. 2014 Oct 30. Palliative Care SAKK 95/06 Blum D, Koeberle D, Omlin A, Walker J, Von Moos R, Mingrone W, deWolf-Linder S, Hayoz S, Kaasa S, Strasser F, Ribi K. Feasibility and acceptance of electronic monitoring of symptoms and syndromes using a handheld computer in patients with advanced cancer in daily oncology practice. Support Care Cancer. 2014 Sep 22.

Presentations San Antonio Breast Cancer Symposium Poster O. Pagani et. al. Advanced HER2 positive breast cancer treated with trastuzumab: is combination with chemotherapy always needed? Randomized Phase III trial SAKK 22/99. K. Matter-Walstra et al. Health economic evaluation of the SAKK Trial 24/09: Safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer. A multicenter, randomized phase III trial.

56th ASH Annual Meeting San Francisco Oral presentation E. Kimby et al. Rituximab plus lenalidomide improves the complete remission rate in comparison with rituximab monotherapy in untreated follicular lymphoma patients in need of therapy. Primary endpoint analysis of the randomized phase-2 trial SAKK 35/10. Poster C. Driessen et al. SAKK 65/08: A Phase I Dose Escalation Study of Bortezomib in Combination with Nelfinavir in Patients with Advanced Hematologic Malignancies.

|www| All SAKK publications can also be found under http://sakk.ch/en/sakk-provides/for-research/scientificpublications/

The Swiss Oncology Research Network

SAKK Newsletter

December 22, 2014  15

IBCSG IBCSG 24-02 SOFT: Efficacy and QoL results presented at SABCS The long awaited results of the efficacy analysis of the SOFT trial were presented by the co-chair Prudence Francis, M.D., Head of Breast Medical Oncology, Peter MacCallum Cancer Centre, Australia, at the San Antonio Breast Cancer Symposium on December 11, 2014. In summary, the addition of ovarian suppression to adjuvant treatment (post-surgery) with tamoxifen reduced breast cancer recurrence in young women with hormoneP. Francis sensitive early breast cancer who received chemotherapy and had not reached menopause. The addition of ovarian suppression to tamoxifen did not benefit all young women. Treatment with tamoxifen plus ovarian suppression reduced the relative risk of developing invasive breast cancer recurrence by 22 % in women who did not transition into menopause after receiving chemotherapy, when compared to treatment with tamoxifen alone. On average, these women were 40 years old when starting hormonal therapy after chemotherapy. A secondary analysis revealed that further benefit could be gained by treating these women with exemestane plus ovarian suppression, which reduced their relative risk of breast cancer recurrence by 35 %, compared to tamoxifen alone, resulting in 7 or 8 fewer women out of 100 having a breast cancer recurrence within 5 years. “These results will change clinical practice,” said Prue. “For the youngest women with hormone-sensitive breast cancer, ovarian suppression will increasingly be recommended. For women who have not reached menopause and have hormone-sensitive breast cancer that carries sufficient risk of recurrence to warrant chemotherapy, doctors are likely to discuss the option of treatment with ovarian suppression plus an aromatase inhibitor as an

alternative to tamoxifen.” SOFT (Suppression of Ovar-

ian Function Trial) was designed to assess the value of ovarian suppression in reducing breast cancer recurrence in young women receiving tamoxifen, and to assess the role of the aromatase inhibitor exemestane plus ovarian suppression in treating young women. Premenopausal women with estrogen and/or progesterone receptorpositive, or hormone-sensitive, breast cancer were randomly assigned to treatment with tamoxifen alone for 5 years, tamoxifen plus ovarian suppression for 5 years, or exemestane plus ovarian suppression for 5 years. SOFT studied these treatments in two different groups of young women with early breast cancer: premenopausal women for whom the physician and patient considered tamoxifen alone without chemotherapy suitable treatment; and women who had already received chemotherapy and remained premenopausal despite chemotherapy. Chemotherapy can suppress production of estrogen by the ovaries and cause menopause, which is associated with reduced recurrence of hormone-sensitive breast cancer. Tamoxifen has been the standard adjuvant hormonal treatment for premenopausal women with hormonesensitive breast cancer. The benefit of adding ovarian suppression to tamoxifen was uncertain. The other treatment investigated, the aromatase inhibitor exemestane, requires suppression of estrogen produced by the ovaries to be effective in premenopausal women. Ovarian suppression was achieved by monthly injections of a GnRH agonist triptorelin (most common choice in SOFT), surgical removal of both ovaries, or radiation of the ovaries. The benefit of adding ovarian suppression to tamoxifen was most pronounced in women younger than 35, an age group at particularly high risk of recurrence. This benefit was even greater with exemestane plus ovarian suppression: after 5 years, 1-in-6 women under age 35 receiving exemestane plus ovarian suppression experienced further breast cancer, compared to 1-in-3 under age 35 receiving tamoxifen alone. SOFT also enrolled premenopausal women whose systemic treatment included only adjuvant hormonal therapy without chemotherapy, as decided with their physician. These women typically were older (average age 46 years), closer to natural menopause onset, and had breast cancer pathology with a more favorable prognosis, compared to women who received chemotherapy. The group who did not receive chemotherapy did very well;

The Swiss Oncology Research Network

16  December 22, 2014

SAKK Newsletter

IBCSG more than 95 % were free from breast cancer recurrence after 5 years with tamoxifen alone. No benefit from ovarian suppression in this group could be detected at this point in time. The results of SOFT were published on-line on the same day in New England Journal of Medicine (see below).

cer, based on age, breast cancer pathology and patient preferences.

Patient-reported quality of life assessed throughout the trial helps to put the treatments into perspective. Karin Ribi, PhD from the quality of life office at the IBCSG Coordinating Center presented the results of these investigations. Mood and physical well-being did not differ between the treatment groups. Although women treated with tamoxifen plus ovarian suppression initially reported worse hormone-related symptoms and sexual functioning than those receiving tamoxifen alone, after 2 years most differences beK. Ribi tween treatment groups were no longer apparent. Effects on sexual functioning were noted throughout the treatment with exemestane plus ovarian suppression.

CLINICAL TRIALS

From these two presentations and the combined analysis of SOFT and TEXT presented in June at ASCO, it can be concluded that, while ovarian suppression is not recommended for everyone, adding it to tamoxifen can reduce breast cancer recurrence in higher-risk patients who remain premenopausal after chemotherapy, particularly in women under the age of 35. Adjuvant treatment with exemestane is more effective than tamoxifen in preventing recurrence when combined with ovarian suppression. Physicians and patients can use these outcomes and the related side effect information to tailor therapy for premenopausal women with hormone-sensitive breast can-

The Swiss Oncology Research Network

The presentations and further abstracts can be found on http://www.ibcsg.org/Public/sabcs2014/Pages/ SABCS2014.aspx

IBCSG 42-12 SNAP The trial evaluates in a randomized phase II fashion three different schedules of nab-Paclitaxel in patients with histologically or cytologically confirmed HER2-negative metastatic (stage IV) breast cancer who have not received any prior chemotherapy. Based on recommendations from the IBCSG Data and Safety Monitoring Committee (DSMC), IBCSG issued an amendment to adapt the dose of nab-Paclitaxel in the induction phase. It was decided to decrease the dose in the induction phase to 125 mg/ m² while keeping the current doses in the maintenance phase. The amendment has to be activated by end of the year 2014. The accrual has increased recently and the accrual goal will be reached at the beginning of 2015. Based on a recommendation from the DSMC, IBCSG has decided to increase the total sample size from 240 to 258. The statistical plan in the protocol requires 76 evaluable patients per arm in order to have, within a reasonable follow-up time, the 63 progression-free survival (PFS) events per arm needed to provide the planned power. The “drop-out” rate of patients who will not contribute to the determination of the primary endpoint PFS has proved to be higher than the originally expected 5%. The rate of non-evaluability, especially for the maintenance phase of the treatment, is anticipated to rise to as much as 12%. To retain the originally planned power, the accrual per arm will therefore be increased to 86. The corresponding amendment is being prepared and will be issued shortly.

IBCSG 48-14/BIG 8-13 POSITIVE The best available evidence suggests that pregnancy after breast cancer does not negatively impact disease outcome and is safe for the offspring but no definitive information is available to recommend a safe interval from BC diagnosis to pregnancy. The POSITIVE trial will investigate

December 22, 2014  17

SAKK Newsletter

IBCSG endocrine therapy (ET) interruption to enable conception for young women between 18 and 42 years of age with endocrine responsive early breast cancer who received adjuvant ET for 18 to 30 months and wish to attempt pregnancy. The main objectives are: • To assess the risk of breast cancer relapse associ ated with temporary interruption of endocrine therapy to permit pregnancy • To evaluate factors associated with pregnancy success after interruption of endocrine therapy. The trial will also allow for the testing of biologic correlates of pregnancy and disease outcome.

A total of 500 patients are planned to be recruited into the trial from centers worldwide in approximately 4 years. The trial is currently being activated in 12 sites in Switzerland. The Institute of Oncology of Southern Switzerland is first site which has opened the trial worldwide, and has accrued the first patient in December.

A psycho-oncological companion study evaluating psychological distress, fertility concerns and decisional conflict in young women who participate in POSITIVE has been developed and will be activated in sites interested and capable to conduct it. The participation of the USAmerican Alliance Group is anticipated and will be negotiated in the months to come.

The complete IBCSG publication list can be downloaded from http://www.ibcsg.org/Member/Publi/IBCSG_Publi/ Pages/default.aspx

Latest IBCSG publication Prudence A. Francis et al. Adjuvant Ovarian Suppression in Premenopausal Breast Cancer. Published online in New Engl J Med on Dec 11.

Rudolf Maibach

IBCSG Coordinating Center (www.ibcsg.org)

Accrual of open clinical trials (As of October 31, 2014) Trials

Current accrual

Current accrual SAKK

Total target accrual

42-12 SNAP

186

51

240

43-09 HOHO

230

60

300

ETOP ETOP Meeting

Clinical trials

The ETOP Annual Meeting was held November 14 – 15 2014 in Vienna, Austria, hosted by the Central European Cooperative Oncology Group (CECOG). Ongoing projects and trials as well as new ideas and concepts were presented and discussed either during the plenary meeting or in the break-out sessions. More than 100 participants from over 20 countries attended the meeting and used the occasion as an opportunity to engage in stimulating high-level scientific exchange with other ETOP participants. These lively discussions continued also during coffee breaks and dinner.

ETOP 2-11 BELIEF BELIEF, a phase II prospective trial sponsored by ETOP and coordinated by the Spanish Lung Cancer Group (SLCG), is the first therapeutic ETOP trial. Rafael Rosell and Rolf Stahel are the chairs and Oliver Gautschi is the co-chair of this trial. The long-term outcome of patients with advanced non-squamous NSCLC with activating EGFR mutations (L858R and exon 19 deletion) treated with the combination of erlotinib and bevacizumab will be tested. An important secondary endpoint of the BELIEF trial is to

The Swiss Oncology Research Network

18  December 22, 2014

SAKK Newsletter

ETOP assess the clinical relevance of the EGFR T790M mutation in a prospective way. Amendment 1 to the BELIEF protocol, which was primarily related to a safety update for bevacizumab and a change in the blood sample preparation, was issued in November 2013 and the centers have subsequently been activated. Accrual was satisfactory and the goal of 102 patients was reached on 9 October 2014, with SAKK sites having enrolled 41 patients. Treatment and follow-up continue as planned.

treatment (chemotherapy) with denosumab as compared to the standard treatment alone in advanced unselected NSCLC treatment-naïve patients. The trial will be conducted in the context of a European collaboration between ETOP and the EORTC, with the latter being the coordinating group. The 1000 patients will be enrolled within approximately 3 years. Center activation is planned for Q1 2015. Nine SAKK sites will participate in this trial. An investigator meeting specifically for SAKK sites was held during the SAKK semi-annual meeting on June 26, 2014.

ETOP/IFCT 4-12 STIMULI

Latest ETOP publications

Thirty percent of patients with small cell carcinoma (SCLC) will have limited stage disease, with a median survival of 16 to 24 months and only 15-25% long term survivors. The combination of chemotherapy and thoracic radiotherapy is currently the standard treatment approach in limited stage SCLC. Several studies have shown that an increased level of immune cells may stop tumor growth. Ipilimumab, a humanized monoclonal antibody, activates the immune system by targeting CTLA-4, a protein receptor that, among others, down-regulates anticancer immune response.

Solange Peters et al., Lungscape: resected non-small cell lung cancer outcome by clinical and pathological parameters. Journal of Thoracic Oncology 9 (11): 1675-1684.

STIMULI is a randomized multicenter open-label trial that tests the efficacy and tolerability of standard treatment alone or with subsequent administration of ipilimumab in patients with limited disease SCLC, with overall survival as primary endpoint. ETOP will conduct the trial in collaboration with the Intergroupe Francophone de Cancérologie Thoracique (IFCT). The protocol has been sent out to the two SAKK sites that will participate, as well as to 32 additional sites in France, Spain, Germany, Belgium, Poland, the Netherlands and the UK. The center activation is ongoing and the first patient was enrolled 28 July 2014. The current accrual is 3 patients.

ETOP 5-12 SPLENDOUR Bone metastases are common in lung cancer and represent a significant cause of morbidity in patients with advanced disease. Denosumab is a monoclonal antibody targeting and inhibiting the RANKL, a protein that acts as the primary signal for bone resorption. The purpose of this study is to investigate the combination of standard

The Swiss Oncology Research Network

Fiona H. Blackhall and Solange Peters et al., Prevalence and Clinical Outcomes for Patients with ALK-Positive Resected Stage I to III Adenocarcinoma: Results From the European Thoracic Oncology Platform Lungscape Project. Journal of Clinical Oncology 32 (25): 2780-7. Simon Patton et al., Assessing standardization of molecular testing for non-small cell lung cancer: Results of a worldwide External Quality Assessment (EQA) scheme for EGFR mutation testing. British Journal of Cancer 111(2): 413-20. The complete ETOP publication list can be reviewed on the ETOP webpage: www.etop-eu.com. Solange Peters Scientific Coordinator Heidi Roschitzki ETOP Coordinating Office (www.etop-eu.org)

December 22, 2014  19

SAKK Newsletter

SWISS CANCER LEAGUE Outstanding researcher receives the Robert Wenner Award 2014

«Cancer Research in Switzerland» report, edition 2014

The Swiss Cancer League awarded Mohamed BentiresAlj, from the Friedrich Miescher Institute for Biomedical Research (FMI), Basel, with the Robert Wenner Award 2014 in November 2014. This researcher convinced the jury with his excellent research work on breast cancer. His innovative and dynamic research has practical clinical applications. Mohamed Bentires-Alj, an outstanding researcher, is also strongly committed to the world cancer community; thus making him the ideal recipient of the Robert Wenner Award.

The seventh edition of the «Cancer Research in Switzerland» report has been published. This publication documents the concerted commitment of the Swiss Cancer Research Foundation, the Swiss Cancer League, as well as the cantonal and regional cancer leagues in funding cancer research in Switzerland. The partner organizations have funded a total of 175 research projects and bursary holders at Swiss universities, institutes and hospitals, as well as academic research organizations and scientific congresses in 2013, with over 20 million Swiss Francs. The new research report shows openly and clearly how the donations are applied to the funding of cancer research. The results of all projects that were completed within the last year, as well as the objectives of this period’s approved research projects are presented in this report. These are highlighted by exciting articles on basic research, clinical, psychosocial and epidemiological cancer research; authored by experts in these four key research domains. This publication is available free of charge in English, German and French, and can be ordered by e-mail to [email protected] It can also be downloaded as a pdf file at: www.swisscancer.ch/researchreport

From left to right: JR. Passweg, president Swiss Cancer League, M. Bentires-Alj, MF. Fey, president of the Scientifc Committee

For further information in German and French visit www.krebsliga.ch/rwp www.liguecancer.ch/prw

Cancer Researcher Nancy Hynes is the new Scientific Committee President as per 2015

14th SWISS BRIDGE Award for Cancer Research SWISS BRIDGE has chosen to grant their award to immunotherapy in oncology research projects. Two researchers have received an award for their projects’ excellence in this area: Professor Laurence Zitvogel, from the Gustave Roussy Comprehensive Cancer Centre, France, and Professor Adrian Ochsenbein, from the Inselspital, Bern University Hospital, Switzerland. Both researchers are sharing the 500 000 Swiss francs award, which is being presented for the 14th time. Their projects have impressed the jury by their relevance and quality in immunotherapy, a very promising research area. Further information: www.swissbridge.ch

N. Hynes Prof. Martin F. Fey, MD, reaches his end term of of-

fice as President of the Scientific Committee (WiKo), yearend 2014. The renowned cancer researcher,

The Swiss Oncology Research Network

20  December 22, 2014

SAKK Newsletter

SWISS CANCER LEAGUE Prof. Nancy Hynes, PhD, Research Group Leader at the

Friedrich Miescher Institute and Adjunct Professor of Molecular Biology at the University of Basel will take over this role. Nancy Hynes has been granted multiple prestigious research awards for her scientific achievements, including the Swiss Cancer League’s Robert Wenner Award. This US citizen has lived in Switzerland since her post doc, in the late 1970s. Although she is not a medical doctor, she has worked intensively with clinicians on the basis of her research topic for many years. The promotion of translational cancer research – making laboratory research findings beneficial to patient treatment – has always been the central focus of her work. Nancy Hynes, who shall retire in Spring 2015, is the ideal person for the office of the WiKo President. Contact Cathy Maret, communication Swiss Cancer League/ Swiss Cancer Research Foundation

[email protected]

12 Breast Centres awarded with Quality Label To date, 12 breast centres in 10 different cantons have been awarded by the Swiss Cancer League (SCL) and the Swiss Society of Senology (SSS) with the quality label for breast centres. Lately, the breast centre of the Geneva university hospitals was also awarded, as the first centre in the canton of Geneva, and third in the French part of Switzerland, after the clinic GSMN in Genolier/Fribourg and the CHUV in Lausanne. Twelve breast centres in Switzerland meet the roughly 100 quality criteria required for the Swiss certificate, and more are soon to follow in 2015. Together with three more centres, which are certified by the German Cancer Society (DKG) or the European Society of Breast Cancer Specialists (EUSOMA), more than half of all the new breast cancer cases (ca. 3000 of 5500) in Switzerland are treated in certified centres. Nevertheless, there are still some regions where patients haven’t yet unrestricted access to a certified centre. For further information in German and French visit www.krebsliga.ch/q-label www.liguecancer.ch/q-label Contact Mark Witschi, MD Head Q-Label Office

[email protected]

The Swiss Oncology Research Network

December 22, 2014  21

SAKK Newsletter

VARIOUS www.cancerdrugs.ch: a website for daily practice www.cancerdrugs.ch is a free website for healthcare professionals for the management of oral tumor therapy. Central to the website is the search function, allowing the fast search for scientific information. Well-founded proposals for prevention and treatment of the most frequently observed adverse event during oral tumor therapy are available. Patient-Information leaflets, which were created in collaboration with the working group “Adhärenz bei oraler Tumortherapie” (compliance during oral tumor therapy, www.oraletumortherapie.ch), can be downloaded in German and French. The content of cancerdrugs.ch is constantly reviewed by medical doctors, hospital pharmacists and oncology nurses. Example: 72 year old female tumor patient with constipation Medication: treatment of non-small cell bronchogenic carcinoma with vinorelbine (initial treatment intravenously administered, subsequently oral administration) since a few days. Symptoms: the patient suffers with severe constipation and complains about difficulty passing stools and flatulence. Status: the patient presents with distention of the upper abdomen and tenderness to touch. Examinations: anamnesis and status survey. Differential diagnosis to exclude acute gastrointestinal obstruction. Question 1: could the symptoms be caused by the vinorelbine treatment? Answer on www.cancerdrugs.ch: Constipation is a very common side effect of vinorelbine treatment (11.4%), which usually manifests within the first few days of treatment. Diagnosis: a correlation between the tumor therapy and the symptoms is highly likely. The diagnosis drug-induced constipation is reached. Question 2: what are the next steps? Answer on www.cancerdrugs.ch: Before treatment with laxatives is initiated impaction and tumor related stenosis resulting in mechanical obstruction should be excluded. Possible substances for the treatment of constipation in tumor patients: - Osmotically acting laxative: Macrogol - Saline laxatives: Magnesium sulphate, sodium sulphate, polyethylene glycol electrolyte solution - Prokinetics: Metoclopramide, neostigmine, prucalopride - Stimulant laxatives: Bisacodyl, sodium picosulfate, senna fruit - Rectal laxatives: stimulant (bisacodyl), saline and osmotic (glycerine), enema (contraindicated in treatment of pa tients with neutropenia and thrombocytopenia) - CAVE: Patients with constipation occurring due to vinca-alkaloid treatment should not be treated with bulking agents or osmotic laxatives. In these cases prokinetics such as metoclopramide are suitable alternatives. Treatment: the patient is treated with metoclopramide three times daily. Course of illness: The symptoms are relieved during treatment. As a general measure liquid intake should be increased in addition to a high-fiber diet and sufficient exercise. Sonia Fröhlich de Moura, [email protected]

The Swiss Oncology Research Network

22  December 22, 2014

SAKK Newsletter

GRANTS, EDUCATION

SAKK / Dr. Paul Janssen Fellowship SAKK and Janssen-Cilag AG have decided to jointly award a fellowship endowed with CHF 30 000.-. The educational grant is aimed at offering young doctors the opportunity to spend three to four months at a renowned research center abroad to gain experience and acquire the necessary know-how and tools to develop and conduct top-quality clinical trials in oncology / hematology . Doctors who train as oncologists / hematologists at Swiss hospitals and are associated with SAKK are herewith invited to apply for the educational grant. The research grant will be awarded at the SAKK semi-annual meeting on June 25, 2015. Submission deadline: April 30, 2015 The SAKK / Dr. Paul Janssen Fellowship regulations can be obtained at (http://sakk.ch/en/sakk-provides/for-research/ research-grants /). Contact: Dennis Ammann, Marketing Manager, [email protected]

CALL FOR IDEAS / Orphan Malignancies Seminar 2015 On 18th September 2014 a multidisciplinary faculty of Swiss experts including surgeons, radiation oncologists, pathologists and oncologists gathered in Zürich, under the chair of Dr. Richard Cathomas, President SAKK Group for Urogenital Tumours, to discuss the management of patients with thymic neoplasms and the optimal treatment of small cell lung cancer. Now we invite researchers to suggest topics for the Orphan Malignancies Seminar 2015 in the field of solid tumors. We encourage researchers to respond to this call for new ideas until 15th January 2015. A two-stage process will be used to identify the most interesting and promising proposals. Thank you very much for sharing your ideas to [email protected]!

The Swiss Oncology Research Network

December 22, 2014  23

SAKK Newsletter

EVENTS Save the date! Public event and press conference on the international clinical trials’ day

May 20, 2015 Join us celebrating 50 years of progress!

SAKK Semi-Annual Meeting June 25/26, 2015, Zurich It is our pleasure to invite you to our semi-annual meeting which will be held in Zurich on June 25/26, 2015. Please visit http://sakk.ch/en/sakk-provides/for-research/semi-annual-meeting for a detailed program and registration form, as well as a floor plan of the premises. Venue: Zurich Marriott Hotel Information: SAKK Coordinating Center Neumuehlequai 42 Effingerstrasse 40 8006 Zürich 3008 Bern Phone: +41 44 360 70 70 Phone: +41 31 389 91 91 Fax: +41 31 389 92 00 E-mail: [email protected] Web: www.sakk.ch

Save the date! 9th Swiss PostASCO June 11, 2015, 09h45-17h00, Bern Information and registration: www.swisspostasco.ch

The Swiss Oncology Research Network

24  December 22, 2014

SAKK Newsletter

EDUCATION, MEETINGS

SAKK Training course for CRCs and CTNs

SAKK Investigators'education

January 29, 2015

March 19 and 26, 2015

Sorell Hotel Ador, Bern

SAKK, Bern

For members of the SAKK network and SPOG the course is free of charge.

For members of the SAKK network and SPOG the course is free of charge.

More information: http://sakk.ch/en/calendar/education/

More information: http://sakk.ch/en/calendar/education/

Supported by

Supported by

Planned in between meetings of project groups and working groups and 2015 Group

Dates Q 1

Breast Cancers

February 26, 2015

Leukemia

March 12, 2015

Lung Cancer

March 12, 2015

New Anticancer Drugs

March 26, 2015

Urogenital Tumors

March 6, 2015

Gynecological Cancer

April 17, 2015

Dates Q 3

September 10, 2015

September 11, 2015

Detailed information regarding time, place and agenda of the meetings can be found on the members'section on our website www.sakk.ch

The Swiss Oncology Research Network

25  December 22, 2014

SAKK Newsletter

SAKK DATES 2015 • • • • • • • • • • •

January 27, 2015, Board Meeting May 5 & 6, 2015, Board Meeting and Retreat May 20, Clinical trials day June 11, 9th Swiss PostASCO Bern June 24, 2015, General Assembly June 25 & 26, 2015 Semi-Annual Meeting Zurich September 1, 2015, Board Meeting September 18, 2015, Orphan Malignancies Seminar November 3, 2015, Board Meeting November 18, 2015, General Assembly November 19 & 20, 2015, Semi-Annual Meeting Zurich

Flag Swiss Group for Clinical Cancer Research Coordinating Center Effingerstrasse 40 3008 Bern Tel. +41 31 389 91 91 Fax +41 31 389 92 00 E-mail: [email protected] www.sakk.ch Claudia Herren [email protected] Peter Brauchli