Newsletter EDITORIAL. Issue 32 September 29, In Brief. Contents

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1 Newsletter Issue 32 September 29, 2014 EDITORIAL 50 years we bring progress to cancer care is celebrating its 50th anniversary in We take advantage of this occasion to look back on our history, celebrate our achievements and set our vision for the future. The anniversary is also an opportunity to express gratitude to our network and our partners and motivate them to continue their commitment to a successful development of. Another goal is the enhancement of s publicity at the relevant target audience wants to be perceived as competent and important institution, holding a leading position in Swiss cancer research. The responsible project manager at the Coordinating Center, Sonja Bill, is already fully engaged in the preparations of the anniversary. An example is the photo shooting which took place at the University Hospital in Bern to develop an specific visual appearance (see p. 3 for the detailed report). Further, a special logo was designed and the following events are scheduled: May 20, 2015 Public event and press conference on the international clinical trials day June 2015 Plenary lecture at the semi-annual meeting in Zurich October 2015 Scientific Symposium with DGHO in Basel November 2015 Symposium at the semi-annual meeting in Zurich In Brief Clinical research how good are we? On 22 and 23 August, the health policy workshop was held in Interlaken for the 19th time on the invitation of Interpharma. President Prof. Beat Thürlimann gave a presentation at this workshop with the topic Clinical research in Switzerland how good are we? PAGE 5 Contents News 2-5 Trial News 6-12 Presentations 13 Publications 14 IBCSG ETOP Cancer League 18 Education, Events 19 Dates, Flag 20 Between these main events, road shows at the centers with series of lectures and individual framework programs are planned. All members of the network and representatives are asked to join us in organizing their regional celebrations in order to introduce and its vision throughout Switzerland. Your inputs and ideas are highly welcome; please send an to sonja.bill. Join us celebrating 50 years of progress! Peter Brauchli, CEO Severin Strasky, Head of Fundraising & Communications

2 2 September 29, 2014 Newsletter NEWS Board decisions At its board meeting on September 2, 2014, in Bern, the Board accepted to conduct the following trials: 25/14, coordinating investigators U. Hasler-Strub, Th. Ruhstaller. Eribulin 1st line in elderly ( 70 years) and old patients (> 80 y) with metastatic breast cancer: a phase II trial Due to a rising number of elderly patients fit for chemotherapy, this trial aims to evaluate an alternative first line therapy regarding efficacy, good tolerability and convenience. In addition, this particular patient population has a high likelihood of comorbidities which prevents the use of standard first-line drugs. Eribulin is well tolerated apart from (manageable) haematological toxicity. It is a synthetic form of a chemotherapeutically active compound derived from the sea sponge halichondria okadai. If this trial proves to be positive, a subsequent randomized phase III trial is foreseen. The trial will be conducted with the support of Eisai. IBCSG 48-14, BIG 8-13, coordinating investigator O. Pagani. A study evaluating the pregnancy outcomes and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy (POSITIVE) The board agreed to participate in this international trial. 33/14 (Beta3_MPN), coordinating investigator R. Skoda. Phase II study to test the effects of beta-3-sympathicomimetic agonists on the disease course and mutant allele burden in patients with myeloproliferative neoplasms This phase II trial is based on the results of a study in mice where myeloproliferative neoplasms (MPN) proved to respond to beta-mimetics (e.g. Mirabegron). It should provide a rapid answer whether targeting the nervous system of the niche cells could be useful for patients with MPN and warrants to be tested in larger and more longterm studies. There is currently no cure for MPN. The approach proposed by Prof. Skoda and his team is novel and fundamentally different from the current strategies, since the primary target of therapy is the correction of the stem cell niche damage, rather than the malignant clone itself. The innovative trial received a grant of the Gateway for Cancer Research/Rising Tide Foundation. 06/13-BOOST, coordinating investigator C. Rentsch. Intradermal BCG immunization before intravesical BCG versus standard intravesical BCG therapy alone in patients with non-muscle invasive bladder cancer. A phase III, randomized, placebo controlled multicenter trial This trial aims at improving cancer vaccine strategies and investigating immune escape mechanisms. Internationally renowned experts in the field of bladder cancer immunotherapy will participate in the trial and address important and novel clinical and research questions. If the trial is successful, the BCG strain used in this trial will become the standard of care strain unless other companies show bio similar activity for other BCG strains. The trial will be conducted in collaboration with the Institut Pasteur and the EORTC within the framework of the EU Programme for Research and Innovation Horizon Development of orteronel stopped The trial 08/11 (orteronel maintenance therapy in patients with mcrpc) was prematurely closed and the development of the trial 08/13 (orteronel maintenance therapy in patients with mcrpc previously treated with novel hormonal agents) had to be stopped as the company ended the development program for orteronel for prostate cancer. Board member election In November, the term of the Board membership of Michele Ghielmini will expire and he has to be (re)elected by the General Assembly on November 19 in St.Gallen. According to the bylaws, the various specialities as well as the regions of Switzerland should be represented in the Board. All specialists active within the network can put forward a candidature for a board membership. Awards and Promotions Member of the board, Arnaud Roth, was nominated as associate Professor at the Faculty of Medicine of Geneva. Arnaud Roth is head physician at the Oncosurgery Unit at the University Hospital in Geneva. Arnaud Roth The following three researchers of our network have been promoted to PD (habilitation): Urban Novak, senior physician oncology at the University Hospital Bern and member of the project groups breast cancer and lymphoma.

3 Newsletter September 29, NEWS Ulf Petrausch, senior physician oncology at the University Hospital Zurich and member of the project groups lung and breast cancer. Martin Zweifel, senior physician oncology at the University Hospital Bern and member of the project groups urogenital cancer, new anticancer drugs and gastrointestinal cancer. CC Staff News Urban Novak As not all Swiss experts in medical oncology are able to attend the ASCO annual meeting, the PostASCO Academy organizes a Swiss PostASCO event in Switzerland every year after the official annual meeting under the patronage of. The PostASCO event allows easy access to scientific news and state of the art interpretation. Program and lectures of the Swiss PostASCO event: New visuals for Within the framework of s 50th anniversary in 2015, the project team decided together with an agency to create a own world of pictures to be used on the website, in the annual report and in various other communication tools. The pictures shall illustrate s functioning and achievements and help to enhance our publicity. Welcome to the team Ulf Petrausch Natascha Backes joined the team as assistant to the CEO. Natascha holds a bachelor of arts in multilingual communication and has several years of experience as executive assistant. Celebrations / Promotions Peter Durrer, head of regulatory affairs and quality assurance and Qiyu Li, biostatistician, both celebrated their five-year-jubilee at the CC. We thank them for their great work and commitment! The University Hospital in Bern kindly allowed the photo shooting on its premises and provided the photographer. Involved were four physicians from our network including a member of the board and eight background actors. The background actors were mainly recruited among family and friends of CC staff. The photo shooting was an exciting experience for all participants and an excellent example for good collaboration between an center, physicians and employees of the coordinating center. For information on job vacancies at, please contact us and/or refer to ASCO news presented in Switzerland On June 12, 2014, in Bern, speakers well-known throughout Switzerland mostly representatives from the Swiss Group for Clinical Cancer Research () presented the scientific results of the annual meeting of the American Society of Clinical Oncology (ASCO) at the Swiss PostASCO event to an audience of specialists and experts. Setting up of a scene The ASCO annual meeting is a leading event in the field of oncology with a strong focus on research and innovation.

4 4 September 29, 2014 Newsletter NEWS CC Office Outing 2014 On August 19, the employees of the Coordinating Center had their yearly company outing. Stéphanie Mohler and Timon Galeazzi, the organizers of this year s trip, had planned a visit to the Trümmelbach waterfalls in the Lauterbrunnen valley. After a pleasant train ride from Bern to Lauterbrunnen train station, a bus took us through beautiful scenery to the waterfalls. With its ten glacial water falls inside the mountain, made accessible by tunnel lift, the Trümmelbach falls are truly unique in Europe and are extremely impressive to see. Trümmelbach alone drains the enormous glacial walls of the Eiger, Mönch and Jungfrau with up to liters of water per second. The visit was followed by a short coffee break in the Trümmelbach restaurant. The journey continued with the Lauterbrunnen-Mürren mountain railway. At the top station started a short hike to the restaurant Winteregg where we had a delicious lunch. It was also a great opportunity to discuss both business and leisurely topics. Those who still had enough energy left decided to descent to Lauterbrunnen by foot. The others took the ropeway. Two colleagues took the descent at a quite leisurely pace and therefore, missed the train back to Bern. However, everyone had a nice time and a beautiful day ended. Timon Galeazzi, Trainee CC timon.galeazzi statistics unit at the Annual Conference of the International Society for Clinical Biostatistics (ISCB) in Vienna From August 24 to 28, 2014, the 35th Annual Conference of the International Society for Clinical Biostatistics (ISCB) took place in Vienna, Austria. Many interesting talks and posters about theory, methods and applications of biostatistics in medical research were presented. The statistics unit was represented with two posters about the topics cluster-randomized trials and phase I trial designs as well as an oral presentation about quantile regression.

5 Newsletter September 29, NEWS Clinical research in Switzerland how good are we? On 22 and 23 August, the health policy workshop was held in Interlaken for the 19th time on the invitation of Interpharma. This year, the theme of the meeting was Transparency challenge and chance, health and social prosperity and the event was attended by around 80 invited guests. President Prof. Beat Thürlimann gave a presentation at this workshop on Clinical research in Switzerland how good are we? In 2013, Switzerland was ranked top worldwide in the innovation index, and in 2011 Switzerland led the world in scientific publications with 3.6 articles per inhabitant (in 2007 it was number 3), followed by Scandinavian countries and the Netherlands. While Switzerland continues to lead the rankings worldwide in many technical and scientific fields on the publications index, it is losing its lead in the life sciences and has even fallen to seventh place in clinical medicine. Switzerland is losing its lead position to other countries. The reasons for this are complex. Prof. Thürlimann referred to factors that have a major influence and are susceptible to control: namely, resources - including finance - and also regulation and implementation. Here it us up to politicians to establish suitable framework conditions, simplifying and above all harmonizing the duration and processes involved in approval procedures and making sure the alignment with international directives, especially OECD standards, are better implemented. But there is also an urgent need for action in the freedom of movement, because research today is international in its focus and Switzerland needs active exchange in order to keep up with the leaders (in research). In addition, however, the new funding models already envisaged for clinical research must also be developed further by exploring new approaches together with industry, government and insurers. According to Stensma (Journal of Clinical Oncology, 2014) the last 20 years have seen an almost 40-fold increase in financial and administrative costs developments that are hurting academic research in particular. But new work and career models have to be created for research physicians, especially for women here the clinics are also called on to come up with more innovative solutions. And last but not least, training and continuing education need to be more interdisciplinary. Only with these measures Switzerland can withstand the global trends that are beyond our control, such as the lower costs with comparable quality in other countries, the presence of new markets (especially Asia, but in the longer term also Africa), high numbers of trial subjects in other countries and the multinational trials that are required. According to Swissmedic, clinical trial activity in Switzerland fell by around 35 % between 2007 and This is also surprising in view of the fact that countries with a similar population size, such as Denmark and Finland, enrol almost five times as many patients in clinical trials for regulatory approval as Switzerland does. The future demands new ideas and models in the performance of clinical trials. In oncology alone, there are more than 300 new molecules in the pipeline, which are suitable as potential new medicines, and this number does not include combinations of different molecules for therapy! Moreover, the achievements in molecular medicine are resulting in the treatment of diseases becoming increasingly personalized. As a result, disease areas are becoming increasingly diversified, and the frequency of a disease and thus patient numbers per indication are decreasing, which is also having an impact on clinical research. With its clinical cancer research network in the shape of the, Switzerland has shown for almost 50 years that it can successfully engage in academic research both on the national and international stage. And the Swiss Clinical Trial Organization (SCTO), which was founded five years ago with its network of Clinical Trial Units (CTUs) is also doing its bit to make sure the quality and attractiveness of (academic) clinical research in Switzerland continue to improve. According to Prof. Thürlimann, therefore, the question how good are we? cannot be answered with the simile of the half full or the half empty glass. It is rather a question of having to make sure the contents of the jug used to refill the glass provides enough fuel (funding) and lubricating oil (regulation). Without innovative and perhaps also progressive political changes in regulation and implementation or in resources, Switzerland will continue to fall back in the global rankings. Claudia Weiss Politics & Development claudia.weiss

6 6 September 29, 2014 Newsletter TRIAL NEWS Trials to be activated 2014 / 2015, effective September 15, 2014 Trial Trial Name Opening of the first site 63/12 Biomarkers in localized prostate cancer (A large serum biobank, prospective trial) Q LungArt (IFCT-EORTC) ETOP SPLENDOUR 23/13 BIG /13 HOVON 132 HOVON 103-tosedostat 06/14 36/13 Alliance/ Prospect trial 33/14 Phase III study comparing post-operative conformal radiotherapy to no post-operative radiotherapy in patients with completely resected non-small cell lung cancer and mediastinal N2 Involvement Survival improvement in lung cancer induced by denosumab therapy. A randomized phase III trial evaluating the addition of deno-sumab to standard first-line anticancer treatment in ad-vanced NSCLC Randomized Controlled Trial to Evaluate the Impact of a Surgical Sealing Patch on Lymphatic Drainage after Axillary Lymph Node Dissection for Breast Cancer A randomised, double blind, parallel group, placebocontrolled multi centre Phase III study to 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 Nelfinavir as Bortezomib-sensitizing drug in patients with proteasome inhibitor-nonresponsive myeloma Randomized study with a run-in dose-selection phase to assess the added value of lenalidomide in combination with standard remission-induction chemotherapy and post-remission treatment in patients aged years with previously untreated acute myeloid leukemia (AML) or high risk myelodysplasia (MDS) (according to IPSS-R risk score > 4.5) 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 therapy in AML and RAEB 66 years and very poor risk AML 18 years A phase I/II open label clinical trial assessing safety and efficacy of intravesical instillation of the recombinant BCG VPM1002 in patients with recurrent non-muscle invasive bladder cancer after standard BCG therapy Combination of Ibrutinib and Bortezomib to treat mantle cell lymphomas patients a multicenter phase I/II trial A phase II/III trial of neoadjuvant folfox, with selective use of combined modality chemoradiation vs. preoperative combined modality chemoradiation for locally advanced rectal cancer patients undergoing low anterior resection with total mesorectal excision Effects of sympathicomimetic agonists on the disease course and mutant allele burden in patients with Jak2-mutatated myeloproliferative neoplasms. A multicenter phase II trial Q Q Q Q Q Q Q Exp. Q Exp. Q Q Q /14 Extended Rituximab with or without Ibrutinib. A randomized blinded Phase II trial Q GRAALL-2014 Treatment of adult acute lymphoblastic leukemia (ALL), evaluating the addition of a second 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 Q2 2015

7 Newsletter September 29, TRIAL NEWS Trials Open for Accrual September 2014 Disease Group Urogenital Urogenital Urogenital Lung Lung Lung Breast Breast Breast Breast Trial Name Trial Description Accrual Target 01/10 96/12 STAMPEDE 15/12 16/08 BELIEF 21/12 22/10 EORTC PRO IBCSG SNAP Involved Node Radiotherapy and Carboplatin Chemotherapy in Stage IIA/B Seminoma Prevention of Symptomatic Skeletal Events with Denosumab Administered every 4 Weeks versus every 12 Weeks A Non-Inferiority Phase III Trial Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy A 5-stage multi-arm randomised controlled trial Early prophylactic cranial irradiation with hippocampal avoidance in patients with limited disease small-cell lung cancer. A multicenter phase II trial Preoperative chemotherapy and radiotherapy with concomitant Cetuximab in non-small cell lung cancer (NSCLC) patients with IIIB disease. A multicenter phase II trial 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 + NSCLC. A clinical trial of ETOP A Phase I and stratified, multicenter Phase II trial of transdermal CR1447 (4-OH-testosterone) in endocrine responsive-her2 negative and triple negative-androgen receptor positive metastatic or locally advanced breast cancer A randomized phase II trial of pertuzumab in combination with trastuzumab with or without chemotherapy, both followed by T-DM1 in case of progression, in patients with HER2- positive metastatic breast cancer EORTC prospective part, Clinical and biological characterization of Male Breast Cancer: an international EORTC, BIG and NABCG intergroup study A randomized phase II study evaluating different schedules of nab-paclitaxel in metastatic breast cancer Current Accrual* Estimated Closure for Accrual Trial Coordinator corinne.rusterholz lukas.stalder@ sakk.ch estelle.cassoly andrea.fuhrer@ sakk.ch vincent.bize christine.biaggi karin.rothgiesser@ sakk.ch marie-aline.gerard 4 estelle.cassoly@ sakk.ch Q Updated *Current accrual as of end of August Accrual for non- trials only includes patients enrolled at centers.

8 8 September 29, 2014 Newsletter TRIAL NEWS Trials Open for Accrual September 2014 Disease Group Breast Trial Name Trial Description Accrual Target IBCSG HOHO Prospective observational study of young women ( 40 years at diagnosis) with breast cancer. Data analyzed will include serial patient surveys and medical record information Leukemias APL 2006 Randomized phase III trial assessing the role of arsenic trioxide and/or ATRA during consolidation course in newly diagnosed acute promyelocytic leukemia (APL) Leukemias EBMT HCT vs CT Compare conventinal chemotherapy to low dose total body irradiation-based conditioning and hematopoietic cell transplantation as consolidation therapy Current Accrual* Estimated Closure for Accrual Trial Coordinator Q fatma.karabulut fatma.karabulut Leukemias CML V Treatment optimization of newly diagnosed 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 Lymphomas 39/10 Nelfinavir and lenalidomide/dexamethasone in patients with progressive multiple myeloma that have failed lenalidomide-containing therapy. A single arm phase I/II trial 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 Lymphomas HD 17 Therapieoptimierungsstudie in der Primärtherapie des intermediären Hodgkin Lymphoms: Therapiestratifizierung mittels FDG-PET Lymphomas REMoDL-B A randomised evaluation of Molecular guided therapy for Diffuse Large B-Cell Lymphoma with Bortezomib (phase III) Lymphomas IELSG-37 A randomized, open-label, multicentre, twoarm 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) katrin.lange michael.beyeler katrin.eckhardt katrin.eckhardt regula.lustenberger simona.berardi 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 simona.berardi Updated *Current accrual as of end of August, Accrual for non- trials only includes patients enrolled at centers.

9 Newsletter September 29, TRIAL NEWS Trials Open for Accrual September 2014 Disease Group Gastrointestinal New Drugs New Drugs New Drugs New Drugs New Drugs Gynaecological heidi.baumgartner Gynaecological Trial Name Trial Description Accrual Target 41/10 65/12 66/12 66/13 67/13 69/13 Mito/ Mango 16b INOVATY- ON Cetuximab monotherapy versus cetuximab plus capecitabine as first-line treatment in elderly patients with KRAS- and BRAF wild-type metastatic colorectal cancer. A multicenter phase II trial Phase I study of LDE225 in combination with Paclitaxel in patients with advanced solid tumors A Phase I, open-label, multi-center, dose escalation study of oral CGM097, a p53/hdm2- interaction inhibitor, in adult patients with selected advanced solid tumors characterized by wild-type TP53 INC280 Combination with BKM120 for glioblastoma patients, Phase I/II trial Phase I study of oral PQR309 in Patients with Advanced Solid Tumors Phase IB of oral BGJ398 (pan FGFR inhibitor) and oral BYL719 (a specific PI3K inhibitor) in adult patients with selected solid tumors A multicenter phase III randomized study with second line chemotherapy plus or minus bevacizumab in patients with platinum sensitive epithelial ovarian cancer recurrence after a bevacizumab/chemotherapy first line Phase III international, randomized study of trabectedin plus Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin plus PLD in patients with ovarian cancer progressing within 6-12 months of last platinum Current Accrual* Estimated Closure for Accrual Trial Coordinator daniela.baertschi milica.enoiu simona.berardi simona.berardi vincent.bize simona.berardi anna.tomaszewska Updated *Current accrual as of end of August, Accrual for non- trials only includes patients enrolled at centers.

10 10 September 29, 2014 Newsletter TRIAL NEWS (effective September 15, 2014) Activated trials Urogenital 96/12 Prevention of Symptomatic Skeletal Events with Denosumab Administered every 4 Weeks versus every 12 Weeks A Non-Inferiority Phase III Trial Activated July 16, 2014 Coordinating investigator Roger von Moos, Chur Clinical project manager lukas.stalder Lung 15/12 Early prophylactic cranial irradiation with hippocampal avoidance in patients with limited disease small-cell lung cancer. A multicenter phase II trial Activated July 11, 2014 Coordinating investigator Hansjörg Vees, Zurich Clinical project manager andrea.fuhrer Breast EORTC PRO EORTC prospective part, Clinical and biological characterization of Male Breast Cancer: an international EORTC, BIG and NABCG intergroup study Activated July 2, 2014 Coordinating investigator Stefan Aebi, Lucerne Clinical project manager estelle.cassoly Authorized trials Urogenital 63/12 Prospective cohort study with collection of clinical data and serum of patients with prostate disease Ethical committee authorization September 11, 2014 Coordinating investigator Daniel Engeler, St.Gallen Clinical project manager vincent.bize Lymphomas 39/13 Nelfinavir as Bortezomib-sensitizing drug in patients with proteasome inhibitor-nonre sponsive myeloma Swissmedic authorization August 18, 2014 Ethical committee authorization August 25, 2014 Coordinating investigator Christoph Driessen, St.Gallen Clinical project manager catherine.berset

11 Newsletter September 29, TRIAL NEWS (effective September 15, 2014) Trials closed for accrual Urogenital 08/11 Orteronel maintenance therapy in patients with metastatic castration resistant prostate cancer and non-progressive disease after first-line docetaxel therapy: a multicenter randomized doub le-blind placebo-controlled phase III trial Closed July 25, 2014 Coordinating investigator Silke Gillessen, St.Gallen & Richard Cathomas, Chur Clinical project manager heike.kenner Lung 19/09 Bevacizumab, pemetrexed and cisplatin, or erlotinib and bevacizumab for advanced non-squamous NSCLC stratified by EGFR mutation status. A multicenter phase II trial including biopsy at progression (BIO-PRO trial) Closed July 17, 2014 Coordinating investigator Oliver Gautschi, Lucerne Clinical project manager lukas.stalder Breast 26/10 Impact of Recurrence Score on Recommendations for Adjuvant Treatment in Patients with ER-positive Breast Cancer Closed July 18, 2014 Coordinating investigator Bernhard Pestalozzi, Zurich Clinical project manager vincent.bize IBCSG A randomized phase III study of radiation doses and fractionation schedules for ductal carcinoma in situ (DCIS) Closed June 23, 2014 Coordinating investigator Guenther Gruber, Zurich Clinical project manager ibcsg38_dcis@fstrf.org Leukemias HOVON 103 Len Randomized multicenter phase II trial with a safety run-in to assess the tolerability and efficacy of the addition of new drugs to standard induction chemotherapy in AML and RAEB >= 66 years Closed August 1, 2014 Coordinating investigator Georg Stüssi, Bellinzona Clinical project manager andrea.fuhrer

12 12 September 29, 2014 Newsletter TRIAL NEWS (effective September 15, 2014) Trials closed for accrual Lymphomas HD 18 Therapieoptimierungsstudie in der Primärtherapie des fortgeschrittenen Hodgkin Lymphoms: Therapie-stratifizierung mittels FDG-PET Closed July 18, 2014 Coordinating investigator Andreas Lohri, Liestal Trial coordinator katrin.eckhardt IELSG-32 Randomized Phase II trial on primary chemotherapy with high-dose methotrexate and highdose cytarabine with or without thiotepa, and with or without rituximab, followed by brain irradiation vs. high-dose chemotherapy supported by autologous stem cells transplantation Closed September 30, 2014 Coordinating investigator Emanuele Zucca, Bellinzona Clinical project manager Gastrointestinal 77/09 A phase I open label/phase II randomized, double-blind, multicenter trial investigating the combination of everolimus and TransArterial ChemoEmbolisation (TACE) with doxorubicin in patients with hepatocellular carcinoma eligible for TACE Closed September 15, 2014 Coordinating investigator Jean-François Dufour, Bern Trial coordinator karin.rothgiesser www All information on trials can also be found under in the members section.

13 Newsletter September 29, PRESENTATIONS Q Abstracts ASTRO 56th Annual Meeting Poster Ghadjar P. et al. Impact of weight loss on survival after chemoradiation for locally advanced head and neck cancer. Secondary results of a randomized phase III trial ( 10/94). ESMO 2014 congress Madrid Oral presentations Pless M.et al. Final results of the 16/00 trial: a randomized phase III trial comparing neoadjuvant chemoradiation to chemotherapy alone in stage IIIA/N2 nonsmall cell lung cancer (NSCLC). Stahel RA. et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial 17/04. Poster discussion Montemurro M.et al. Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumors: A multicenter two stage phase II trial 56/07. Poster Templeton A. et al. Prevention of symptomatic skeletal events with denosumab administered every 4 weeks versus every 12 weeks-a non-inferiority phase III trial: 96/12 - REDUSE. Rothschild S. et al. Prospective evaluation of circulating VEGF in patients with advanced nonsmall cell lung cancer treated with bevacizumab, pemetrexed and cisplatin in the trial 19/09. Matter-Walstra K. et al. Health economic analysis of the randomized multicenter phase II trial 77/08: sorafenib with or without everolimus in patients with unresectable hepatocellular carcinoma (HCC).

14 14 September 29, 2014 Newsletter PUBLICATIONS Q Urogenital STAMPEDE Attard G, Sydes MR, Mason MD, Clarke NW, Aebersold D, de Bono JS, Dearnaley DP, Parker CC, Ritchie AW, Russell JM, Thalmann G, Cassoly E, Millman R, Matheson D, Schiavone F, Spears MR, Parmar MK, James ND. Combining Enzalutamide with Abiraterone, Prednisone, and Androgen Deprivation Therapy in the STAMPEDE Trial. Eur Urol Jun 27. Leukemia GRAALL-2003/2005 Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, Thomas X, Cayuela JM, Grardel N, Chalandon Y, Boissel N, Schaefer B, Delabesse E, Cavé H, Chevallier P, Buzyn A, Fest T, Reman O, Vernant JP, Lhéritier V, Béné MC, Lafage M, Macintyre E, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood Jun 12. www All publications can also be found under Lymphoma 35/98 Lee CS, Ashton-Key M, Cogliatti S, Rondeau S, Schmitz SF, Ghielmini M, Cragg MS, Johnson P. Expression of the inhibitory Fc gamma receptor IIB (FCGR2B, CD32B) on follicular lymphoma cells lowers the response rate to rituximab monotherapy ( 35/98). Br J Haematol Aug 21. Gastrointestinal Cancer 40/87 Käser SA, Froelicher J, Li Q, Müller S, Metzger U, Castiglione M, Laffer UT, Maurer CA. Adenocarcinomas of the upper third of the rectum and the rectosigmoid junction seem to have similar prognosis as colon cancers even without radiotherapy, 40/87. Langenbecks Arch Surg Aug /00 Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P, Roth AD, Klingbiel D, Bosman F, Delorenzi M, Tejpar S. Distal and proximal colon cancers differ in terms of molecular, pathological and clinical features. Ann Oncol Jul 23. IBCSG Clinical trials IBCSG SNAP A randomized phase II study evaluating different schedules of nab-paclitaxel in metastatic breast cancer. 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. The acrynom stands for Schedules of NAb-Paclitaxel. It is planned to recruit 240 patients within about 30 months. SNAP evaluates three schedules of nab-paclitaxel as prolonged chemotherapy administration strategy. All three arms start with a common induction treatment during the first three cycles, and then continue with different schedules of reduced dose intensity until progressive disease or lack of tolerability. Each of the three arms will be compared to a historical reference of seven-month median PFS based on the most recent trial with Docetaxel as control arm to determine whether any of the three arms are worthy of further investigation. The trial is being conducted in several European countries. The first patient was randomized in April 2013, and by July 31, 2014, 131 patients have been recruited. Nine sites participate, and recruited 32 patients until July. Based on recommendations from the IBCSG Data and Safety Monitoring Committee (DSMC), IBCSG has decided to adapt the dose of nab-paclitaxel in the induction phase, and asks to carefully consider comorbidities when screening new patients.

15 Newsletter September 29, IBCSG The DSMC noted that few patients completed the three cycles of induction regimen without dose modification. The actually administered doses among those who had dose modification correspond to a dose level of about 125 mg/m² given 3 out of 4 weeks. Moreover, investigators are facing many logistical problems related to the frequent dose delays. For patients, these dose delays and dose reduction are sometimes associated with psychological problems because these events induce stress. They do not receive the treatment as expected and may think that dose reductions result in insufficient treatment. Consequently, IBCSG has decided to decrease the dose in the induction phase to 125 mg/m² while keeping the current doses in the maintenance phase. The induction phase foresees only one dose reduction level (to 100 mg/m²) now. Dose reduction tables for both the induction and the maintenance phase of the treatment have been adapted and simplified. The amendment also contains an update of the safety information on nab-paclitaxel. In addition, a warning concerning the use of concomitant CYP2C8 or CYP3A4 inhibitors or inducers has been included. The corresponding amendment has been issued and will have to be activated within a period of 120 days. IBCSG s Program for Young Patients IBCSG HOHO Prospective observational study of young women (< or = 40 years at diagnosis) with breast cancer. Data analyzed will include serial patient surveys and medical record information. IBCSG is the Young Women s Breast Cancer Study, and HOHO stands for Helping Ourselves Helping Others. It is a longitudinal cohort study of 300 young women with breast cancer (early or advanced) in selected institutions in Europe. All eligible patients treated at each center are invited to join the cohort. Patient surveys and medical record review are utilized. Women are surveyed every six months for the first three years after diagnosis, then yearly thereafter for an additional seven years (for a total follow-up of 10 years following diagnosis). The study has two main objectives: 1. To identify in selected institutions in Europe a cohort of young women (age 18-40) newly diagnosed with breast cancer (early or advanced) to assess a broad range of variables at baseline and over the course of the ensuing 10 years. 2. To characterize this population at diagnosis and in follow-up regarding disease and psychosocial outcomes (e.g., presentation and disease characteristics, fertility and menopausal issues, and long term outcome). At present, 12 centers in Italy and four centers in Switzerland are participating in the trial and have accrued 222 patients up to end of July 2014, 57 of them by Swiss sites. IBCSG 48-14/BIG 8-13 POSITIVE A study evaluating the pregnancy outcomes and safety of interrupting endocrine therapy for young women with endocrine responsive breast cancer who desire pregnancy (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 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. Accrual of open clinical trials (As of July 31, 2014) Trials Current accrual Current accrual Total target accrual SNAP HOHO

16 16 September 29, 2014 Newsletter IBCSG The main objectives are: 1. To assess the risk of breast cancer relapse associated with temporary interruption of endocrine therapy to permit pregnancy. 2. 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 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 US-American Alliance Group is anticipated and will be negotiated in the months to come. A total of 500 patients are planned to be recruited into the trial from centers worldwide in approximately four years. The trial activation package has been sent to more than 60 interested sites and all IBCSG centers on July 3. There is a high interest of members in this trial. Ten sites have announced their participation. The activation is currently ongoing. Latest IBCSG publications Senkus E, Gomez H, Dirix L, Jerusalem G, Murray E, Van Tienhoven G, Westenberg AH, Bottomley A, Rapion J, Bogaerts J, Di Leo A, Neškovi-Konstantinovi Z. Attitudes of young patients with breast cancer toward fertility loss related to adjuvant systemic therapies. EORTC study BIG Psychooncology 23: , (IBCSG 29-03). The complete IBCSG publication list can be downloaded from Pages/default.aspx Rudolf Maibach IBCSG Coordinating Center ETOP The specific aims of the European Thoracic Oncology Platform (ETOP) is to promote research in the field of thoracic malignancies in Europe by sponsoring and/or performing own multicenter studies, fostering scientific exchange on laboratory and clinical issues among interested parties and serving as meeting platform for European study groups. In this issue we would like to report on the current status of the running and upcoming ETOP trials, the 3rd ETOP Residential Workshop and the latest publications. Clinical trials 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. BELIEF will determine the long-term outcome of patients with advanced non-squamous NSCLC with activating EGFR mutations (L858R and exon 19 deletion) with or without T790M mutation at diagnosis and treated with the combination of erlotinib and bevacizumab. The trial was opened in the network in June 2012 with the enrollment of the first patients. Amendment 1, 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. By the end of August 2014, sites have enrolled 38 patients. SLCG (Spain), ICORG (Ireland) and sites in Greece and Italy also participate in the trial. The total accrual by the end of August 2014 is 100 patients and we assume to reach the recruitment goal of 102 patients by the end of ETOP/IFCT 4-12 STIMULI 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 % long term survivors. The combination of chemotherapy and thoracic radiotherapy is currently the standard treatment approach in limited stage SCLC.

17 Newsletter September 29, ETOP Several studies now showed 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 downregulates the immune system. The STIMULI trial tests the efficacy and tolerability of the 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). Center activation has started in July 2014 and the first patient was enrolled on July 28, Two sites will participate. 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 that targets and inhibits 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 treatment (chemotherapy) with denosumab as compared with the standard treatment alone in advanced unselected NSCLC treatment-naïve patients. This trial is currently in the activating process. The trial will be conducted in the context of a strong and unique European collaboration between ETOP and the EORTC, with the latter being the coordinating group. The 1000 patients will be enrolled within approximately three years. and several other cooperative groups from all over Europe will participate in this trial. The first centers will be activated in September ETOP Meeting The ETOP Annual Meeting will take place on November 14 to 15, 2014, in Vienna, Austria. The program and registration form can be downloaded from the ETOP website: The registration is open until September 10, experts contributed presentations in their field of expertise in cancer therapy, molecular testing and conduct of clinical trials. As selected hot topics, the hosts presented a cross-european comparison of lung cancer care pointing out the connection between the 5-year survival and the economic power of a country and a new cancer intervention plan to improve the situation in Poland. In addition, the participants were asked to bring their own research project. These projects were presented and discussed in four different groups, each chaired by one or two senior scientist from the faculties. The many excellent presentations were followed by lively discussions that continued over coffee breaks and dinners. The workshop was financed by ESMO through an educational grant and the generous support from Roche and Amgen. Many thanks also go to Kathleen Beese and Alicja Maciejewska-Izdebska for their great effort and a perfect organization of the workshop. We certainly look forward to continuing the tradition of the ETOP Residential Workshops and to meet you next time. Latest ETOP publication Fiona H. Blackhall, Solange Peters, et al., (2014) Prevalence and clinical outcomes for patients with ALK-positive resected stage I-III adenocarcinoma: Results from the ETOP Lungscape Project. Journal of Clinical Oncology.32 (25): The complete ETOP publication list can be reviewed on the ETOP website: Solange Peters Scientific Coordinator Heidi Roschitzki ETOP Coordinating Office ( ETOP Residential Workshop in Gdansk, Poland The 3rd ETOP Residential Workshop was held on August 27 to 29, 2014, in Gdansk, Poland. Thirty two young thoracic oncology investigators from 14 countries attended the workshop. The overall program focused on current trends in research and cancer care and 17 lung cancer

18 18 September 29, 2014 Newsletter SWISS CANCER LEAGUE Cancer Conference 2014: Radon The Underestimated Risk in Living Spaces The Swiss Cancer League and the Swiss Federal Office for Public Health s Cancer Conference 2014 is dedicated to radon issues. Radon is a natural radioactive inert gas which can enter a building through cracks and holes in its foundation. New risk assessments show that elevated radon concentrations inside buildings could occur in all regions of Switzerland. Radon annually causes between 200 and 300 deaths due to lung cancer in Switzerland. This figure is comparable to the number of deaths caused by melanoma. Radon is second only to smoking as the leading cause of lung cancer. Radon is even the largest risk factor of lung cancer for non-smokers. By taking appropriate measures in new and converted buildings, radon exposure indoors can be significantly reduced, with little effort. Specialists from the building, science and medical sectors shall shed light on this issue through different perspectives. Measures to reduce radon indoors, as well as the consequences of the new framework conditions in both law and construction standards shall be presented and discussed. The Cancer Conference 2014 shall conclude with a panel discussion in which Dr. Roland Charrière, Deputy Director of the Swiss Federal Office for Public Health and Professor Dr. Jakob Passweg, President of the Swiss Cancer League shall participate, along with other experts. The Conference is aimed at professionals and those interested in medicine, public health, construction and science, as well as governmental staff, homeowners and notaries. Eight credits are awarded by the Swiss Society of Physicians for Prevention and Health Care (SGPG). 11 Breast Centres awarded with Quality Label In July 2014, the Swiss Cancer League (SCL) and the Swiss Society of Senology (SSS) awarded their quality label to the breast centre of the university hospital of Berne at the Inselspital. And in September 2014, the breast centre of the cantonal hospital of Winterthur was also awarded. Both centres are the first ones in their cantons to receive this label. In both breast centres the focus is placed on interdisciplinary collaboration amongst the various disciplines at the centre, as well as with other units within the hospital, with external partners and private physicians. Together, gynaecologists, radiologists, pathologists, surgeons, oncologists, as well as plastic surgeons, and other medical specialists coordinate their efforts for a most efficient and high-quality diagnostic, treatment and follow-up of breast cancer patients. Only two years after the first certification, already eleven breast centres in Switzerland meet the roughly 100 quality criteria required for the Swiss certificate, and more are soon to follow. For further information in German and French visit Contact Mark Witschi, MD Head Q-Label Office q-label@krebsliga.ch The Cancer Conference 2014 s programme, registration procedures and further information can be found at: WHEN: 4 December 2014, 9:15 a.m. 4:30 p.m. WHERE: Hotel National Hirschengraben 24, 3011 Bern FEE: Fr. 80. CONTACT: Dr. Patrizia Frei Swiss Cancer League Tel krebstagung@krebsliga.ch

19 Newsletter September 29, EDUCATION, EVENTS Project Groups Timetable Investigators' Education October 23 & 30, 2014 Bern For members of the network and SPOG the course is free of charge. More information: Supported by Semi-Annual Meeting November 20/21, 2014, St.Gallen It is our pleasure to invite you to our semi-annual meeting which will be held in St.Gallen on November 20/21, Please visit for a detailed program and registration form, as well as a floor plan of the premises. Venue: Hotel Einstein Information: Coordinating Center Berneggstrasse 2 Effingerstrasse St. Gallen 3008 Bern Phone: Phone: Web: Fax: Web: events