A Phase 1b/2 Study of Imatinib in Combination With Everolimus in Synovial Sarcoma
I. To determine the maximum-tolerated dose (MTD) of everolimus in combination with imatinib
mesylate in patients with synovial sarcoma. (Phase I) II. To determine the overall response
rate (RR = CR + PR). (Phase II)
I. To determine RR, progression-free survival (PFS), and overall survival (OS). (Phase I)
II. To determine predictors of response. (Phase II) III. To obtain tissue biopsy and plasma
samples for correlative studies pre- and post-treatment. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of everolimus followed by a phase II
Patients receive everolimus orally (PO) once daily and imatinib mesylate PO once daily on
days 1-28. Course repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Patients undergo blood and tumor tissue sample collection at baseline and
periodically during study for correlative biomarker and protein expression studies.
After completion of study therapy, patients are followed up for 30 days.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) of everolimus in combination with imatinib mesylate determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 3.0 (Phase I)
DLT is defined as the occurrence of any unexpected Grade 3 non-hematologic toxicity including diarrhea (despite use of antidiarrheal prophylaxis or glucocorticoids), or nausea and vomiting (despite use of maximal anti-emetics), and any Grade 4 toxicity.
Mary Louise Keohan
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|