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DATECAN PROJECT 1 Guidelines for endpoint definitions in cancer trials Bonnetain F DATECAN Project on behalf DATECAN steering committee Statisticians from.

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Presentation on theme: "DATECAN PROJECT 1 Guidelines for endpoint definitions in cancer trials Bonnetain F DATECAN Project on behalf DATECAN steering committee Statisticians from."— Presentation transcript:

1 DATECAN PROJECT 1 Guidelines for endpoint definitions in cancer trials Bonnetain F DATECAN Project on behalf DATECAN steering committee Statisticians from CRLCC, EORTC, FFCD : Bellara C, Collette L, Dousseau A, Gourgou S, Kramar A, Ouali M, Mathoulin S

2 DATECAN PROJECT 2 Rationale Review of randomized clinical trials in oncology(Mathoulin et coll. JCO 2008) Medline databases 2004: Cancer / Randomised Clinical Trial : 8 journals: Lancet, JAMA, BMJ, NEJM / BJC, JCO, JNCI, Cancer Review of phase II (11) and phase III (104) randomized clinical trials 1) Heterogeneity in the selection of ‘survival’ endpoints 2) Non-optimal survival endpoint definition 184 defined survival endpoints among 104 phase III trials N% Overall survival10155 Progression-free survival2715 Disease-free survival1810 Time to progression169 Relapse-free survival105 Event-free survival126

3 DATECAN PROJECT 3 Rationale

4 DATECAN PROJECT 4 Rationale

5 DATECAN PROJECT 5 Rationale

6 DATECAN PROJECT 6 Definitions of guidelines in publications: Without formal consensus (rather expert opinion) Not often used Available for only few cancer sites Heterogeneity in: The selection of time to event (survival) endpoints The definitions of these endpoints Summary

7 7 Events contributing to DFS in adj Colon Cancer Locoregional recurrenceEE Distant metastasesE E Second primary, same cancerE E Second primary, other cancer IE (Second primary, colorectal)E E Death from same cancerE E Death from other cancerE E Non-cancer related deathE E Treatment related deathE E Loss to follow-upCC MOSAIC/PETACC8 PETACC-3/ACCORD-02 DFS definitions MOSAIC/PETACC8 relapse, death, 2 nd colorectal cancer 2 nd cancer other than colorectal (ignored) PETACC-3/ACCORD-02 relapse, death, 2 nd colon cancer 2 nd cancer other than colon (event / RFS including only 2 nd colon cancer)

8 DATECAN PROJECT 8 Consequences  Difficulties of interpretation Comparison between trials Different conclusions according to different definitions Example: PETACC 03 (Van Cutsem E et al. J Clin Oncol 2009) (irinotecan / 5-fluorouracil (5-FU) / folinic acid (FA) versus 5-FU/FA in stage III colon cancer) DFS (with second primary tumors)  Significant difference DFS (without second primary tumors)  Non significant difference Summary

9 DATECAN PROJECT 9 Objective To develop guidelines for survival endpoints definitions  standardization: 1. To define terminology 2. To define events and censoring process

10 DATECAN PROJECT 10 Methods 1. Identification of selected cancer sites and relevant endpoints, based on literature review 2. For each cancer site Develop guidelines with: Consensus methods based on expert opinion obtained in a systematic manner European consultation Consultation of experts with various backgrounds (oncologist, surgeon, radiotherapist, biostatistician, …) Later contact EMEA etc..

11 DATECAN PROJECT 11 Target cancer sites First year 2010 - 2011 Sarcomas Pancreas cancer Breast cancer Following years: Colo-Rectal cancer GI cancer (Stomach) ± oesophagus Kidney & Bladder cancer Lymphomas Head & Neck cancer Lung cancer

12 DATECAN PROJECT 12 Consensus method

13 DATECAN PROJECT 13 Example of questionnaire (GI) Totally disagree Totally agree 123456789 Local relapse/recurrence Regional Relapse/recurrence Appearance/occurrence of distant metastases Appearance/occurrence of liver metastases Appearance/occurrence of non liver metastases Second pancreatic cancer Second non pancreatic cancer Death related to primary cancer Death related to a second cancer Death related to protocol treatment Other cause of death Unknown cause of death End of treatment due to… Occurrence of grade 3-4 WHO PS Loss of follow up Other : specificy and score 1.Should the following clinical events be regarded as events in the definition of the endpoint Disease Free survival (DFS)? Please place one tick on each line. Table 2 (Setting “ no detectable disease ” only)

14 DATECAN PROJECT 14 NameSpecialtyGroupGroup / Committee Laurence ColletteBiostatisticsEORTC Headquarters DATECAN Steering Committee pancreatic cancer pilot Group Franck BonnetainEpidemiology, BiostatisticsCGFL & FFCD & GERCOR DoussauEpidemiology, BiostatisticsINSERM & CHRU Karin HaustermansRadiation oncologistEORTC ROG, ESTRO pancreatic cancer pilot Group Bengt GlimeliusMedical oncologistNordic GI- group /Swedish pancreatic group/ EORTC GI Bert BonsingSurgical oncologistESSO Jean Luc Van LaethemGI OncologistEORTC GI + BGDO (Belgian Group of Digestive Oncology) Thierry ConroyMedical oncologistFNCLCC/ PRODIGE/EORTC GI Francois LacaineSurgical oncologistFRENCH Manfred LutzMedical oncologistEORTC GI pancreatic cancer Scoring Committee Daniela AustGI PathologistEORTC GI Voker BudachRadiation oncologist ROG EORTC Groups Harun BadakhshiRadiation oncologist ROG EORTC Groups Oscar MatzingerRadiation oncologistMember of GI and ROG EORTC Groups Erich GerberRadiation oncologistROG EORTC Groups Alain HendliszMedical oncologistEORTC GI Geertjan van TienhovenRadiation oncologistDutch pancreatic Biliary Cancer Group & EORTC ROG Roberto LabiancaMedical oncologistEORTC GI/ GIVIO (Italy) Josep TaberneroMedical oncologistEORTC GI/ TTD (Spain) Teresa MacarullaMedical oncologistEORTC GI / TTD (Spain) Marcel Den DulkSurgical oncologistEORTC GI David CunninghamMedical oncologistUK Hans Joachim SchmollMedical oncologistAIO, EORTC GI John P. NeoptolemosSurgical oncologistNCRI/ESPAC Claudio BassiSurgical oncologistESPAC Christos DervenisSurgical oncologistESPAC Debbie DevinecliniciansNCRI/ESPAC Seema ChauhancliniciansNCRI/ESPAC Charlotte RawcliffecliniciansNCRI/ESPAC Paula GhanehcliniciansNCRI/ESPAC Trevor CoxBiostatisticianNCRI/ESPAC Muriel MauerBiostatisticianEORTC Headquarters Matthias KarraschClinicianEORTC Headquarters Emmanuel Mitry Gastro-intestinal oncologist FFCD/AGEO/EORTC GI Laetitia Dahan Gastro-intestinal oncologist FFCD Thomas Aparicio Gastro-intestinal oncologist FFCD/AGEO Philippe Rougier Gastro-intestinal oncologist FFCD/EORTC GI Michel DucreuxMedical oncologistFNCLCC/ EORTC GI David MalkaMedical oncologistFNCLCC/AGEO Adenis AntoineMedical oncologistFNCLCC/PRODIGE Dromain ClarisseMedical oncologistFNCLCC Julien TaiebGastro-intestinal oncologistAGEO/FFCD Benoist ChibaudelMedical oncologistGERCOR Aimery de GramontMedical oncologistGERCOR Pascal HammelGastro-intestinal oncologistGERCOR/FFCD Jean Robert DelperoSurgical oncologistFRENCH/FNCLCC Alain SauvanetSurgical oncologistFRENCH Patrick PessauxSurgical oncologistFRENCH Christophe HennequinRadiation oncologistSFRO Alice MegeRadiation oncologistSFRO David AzriaRadiation oncologistSFRO Veronique GirreMedical oncologistGERICO Emmanuel BlotMedical oncologistGERICO Cécile MertensMedical oncologistGERICO Lionel UwersMedical oncologistGERICO Aurélien LatoucheBiostatistician EpidemologistRFUEC Valérie JoosteBiostatisticianFrancim Virginie BergerBiostatistician and clinicianGroup of CRLCC statisticians Emmanuel ChamoreyBiostatisticianGroup of CRLCC statisticians Sophie DussartBiostatisticianGroup of CRLCC statisticians Jocelyn GalBiostatisticianGroup of CRLCC statisticians

15 DATECAN PROJECT 15 EORTC Group contribution To provide list of experts:  For participation in the design of the questionnaire (2-3)  Inclusion criteria  Experience in the specialty (>15 years: yes / no)  Principal investigator in clinical trials (>3: yes / no)  Participation in research projects (>3 : yes / no)  Publications in the specialty (>3: Yes / No)  For completion of the questionnaire (15-20)  Inclusion criteria  Experience in the specialty (>10 years: yes / no) (not strict)  Principal investigator in clinical trials (>1: yes / no)  Participation in research projects (>1 : yes / no)  Publications in the specialty (>3: Yes / No)

16 Schedule January 2010 – May 2010 List and agreement of expert for Pilot Group and RC for Pancreatic, Sarcoma and Breast May – Sept 2010 Creation of questionnaire forms Validation and pre-test by pilot group (ongoing for breast) Database constitution and validation (e-crf) Since Nov 2010 First round consensus for Pancreatic and Sarcoma DATECAN PROJECT 16


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