SARC009: Phase 2 study of dasatinib in patients with previously treated, high‐grade, advanced sarcoma

摘要: BACKGROUND Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial dasatinib patients with advanced sarcoma. METHODS Patients received twice daily. primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial within 6 months stable disease duration ≥6 months) target ≥25%. Patients were enrolled into 1 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor Bayesian hierarchical design. For each subtype, enrollment stopped after minimum 9 treated if there <1% chance CBR ≥25%. RESULTS A total 200 enrolled. Accrual early 5 because low CBR. leiomyosarcoma (LMS) undifferentiated pleomorphic sarcoma (UPS) fully accrued 47 42 evaluable patients, respectively, benefit. probability that ≥25% LMS UPS 0.008 0.10, respectively. median progression-free survival ranged from 0.9 rhabdomyosarcoma 2.2 LMS. overall 8.6 months. most frequent adverse events constitutional, gastrointestinal, respiratory, 36% required dose reduction toxicity. Serious attributed therapy occurred 11% patients. CONCLUSIONS Dasatinib may have but is inactive as single agent other subtypes included herein. design allowed termination accrual lack drug activity. Cancer 2016;122:868–74. © 2015 American Society.