Randomized Trials of Adjuvant Imatinib and Chemotherapy for GIST and Soft Tissue Sarcomas
This document summarizes current and recently closed trials regarding gastrointestinal stromal tumors (GIST) and soft tissue sarcomas. Key trials include a randomized controlled trial evaluating the effectiveness of adjuvant imatinib mesylate (Glivec) versus no further therapy post-surgery for completely resected, intermediate/high-risk GIST. Other studies explore chemotherapy options for advanced sarcomas. The trials aim to assess overall survival, relapse-free survival, and treatment toxicity, contributing valuable data to the field of oncology.
Randomized Trials of Adjuvant Imatinib and Chemotherapy for GIST and Soft Tissue Sarcomas
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Presentation Transcript
STBSG – Current & recently closed trials CTOS 2005
PROTOCOL 62024: Intermediate and high risk localized, completely resected, gastrointestinal stromal tumors (GIST) randomized controlled trial of adjuvant imatinib mesylate (Glivec) versus no further therapy after complete surgery Collaborating Groups: ISG, FSG, EORTC STBSG, GEIS, AGITG Study Coordinators: P. CASALI, Milan (ISG) and J-Y BLAY, Lyon (EORTC STBSG) • Eligibility: • GIST with positive immunostaining for KIT • Risk of relapse documented on surgical specimen • No evidence of residual macroscopic disease after surg • No distant metastases • WHO PS 0-2, age >17 • No prior radiation therapy /chemotherapy • Stratification: • Risk category • Tumour site • Resection level • Main endpoint: • Overall survival • Secondary endpoints: • Relapse-free survival • Relapse-free interval • toxicity
PROTOCOL 62022: Phase II study of Iressa (ZD1839) in locally advanced and/or metastatic synovial sarcoma Study Coordinator: J-Y Blay, Lyon ZD1839 500 mg/day orally once a day • Eligibility: • Advanced/metastatic synovial sarcoma expressing HER1 Ag • Frozen tissue available for genetic confirmation of the diagnosis and molecular analysis • One previous line of chemotherapy containing doxorubicin and/or ifosfamide
Study 62022Efficacy evaluation * 4 Patients with stable disease at week 12
PROTOCOL 62012: Randomized trial of single agent doxorubicin versus doxorubicin plus ifosfamide Study Coordinator: I. Judson, London • Eligibility: • High grade STS (2-3) • Age 16-60 • No previous chemo for adv/met disease • WHO PS < 2 • Stratification: • Age (<50 vs ≥50) • PS (0 vs 1) • Liver mets (0 vs +) • Histological grade (2 vs 3)
62012Interim analysis and stopping rule • Stopping rule for toxicity • Stop if febrile neutropenia in 30% of the cycles • Documented cycles (Dox-Ifos): 114 • Cycles with febrile neutropenia: 25 (22%) • Interim analysis • 1st interim analysis after 52 progressions / deaths • Aim: to detect a doubling in 6-months PFS rate • 44 events have been recorded so far • Interim analysis foreseen in November
PROTOCOL 62981: Randomized Phase III study to evaluate the role of high dose chemotherapy intensification in the treatment of intermediate prognosis Ewing’s sarcoma and PrimitiveNeuroectodermal Tumour (PNET) Study Coordinator: I. Judson, London • VIDE: • Vincristine • Ifosfamide • Doxorubicin • Etoposide • Eligibility: • Ewing/PNET • < 50 years • No previous chemo Local therapy • VAI: • Vincristine • Actinomycin • Ifosfamide • Stratification: • Age • Local treatment • VAC: • Vincristine • Actinomycin D • Cyclophosphamide • Bu-mel: • Busulfan • Melphalan
PROTOCOL 62991-22998:Phase II study of moderate dose radiotherapy for inoperable aggressive fibromatosis Study coordinator: Ronald KEUS, Arnhem • Eligibility: • Histologically confirmed aggressive fibromatosis • Measurable disease (RECIST) • No current endocrine or chemotherapy, no prior or concurrent limb perf with TNF • >15 years
Study 62027 Phase II study of Glivec (Imatinib) in locally advanced and/or metastatic soft tissue sarcomas expressing the t(17;22)(q22;q13) translocation resulting in a COL1A1/PDGF- fusion protein i.e DermatoFibroSarcoma Protuberans (DFSP) and Giant Cell Fibroblastoma (GCF) Treatment scheme: Imatinib 400 mg bid least 14 weeks until progression or unacceptable toxicity Study Coordinator: Professor Allan van Oosterom, Leuven, Belgium
EORTC 62961-ESHO RHT-95 study of neoadjuvant chemotherapy +/- regional hyperthermia REGISTRATION EVALUATION RESPONSE EIA 115+RHT 101 EIA 124+RHT 121 EIA 120+RHT 112 EIA 112+RHT 93 Arm A: Arm B: 13th week EIA 124 EIA 118 EIA 109 EIA 106 RADIOTHERAPY RESECTION SURRGICAL EIA 67+RHT 53 EIA 65+RHT 50 EIA 60+RHT 44 EIA 53+RHT 36 ResponderCR, PRorStable Disease Arm A: Arm B: FU EIA 58 EIA 54 EIA 47 EIA 45
Trial 62043: Phase II trial of angiogenesis inhibitor GW786034 Study Coordinator :Pr Jaap Verweij (Rotterdam, NL) • Oral GW786034 – inhibitor of VEGFR-1, VEGFR-2, VEGFR-3 • 800 mg PO once daily • Primary end-point progression-free survival at 12 weeks • Secondary end-points: overall PFS, response, overall survival, toxicity
Scope for collaboration • Dox v Dox/ifos study if IDMC report due end November recommends study continues • Future trials in rare subtypes • Urgent need to solve barriers to EORTC / SARC intergroup collaboration We’re working on it!
