A Phase 1b/2 Study of Imatinib in Combination With Everolimus in Synovial Sarcoma
Overview
- Phase
- Phase 1
- Intervention
- diagnostic laboratory biomarker analysis
- Conditions
- Adult Synovial Sarcoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Response Rate (CR + PR) Assessed by RECIST 1.1 (Phase II)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase I/II clinical trial is studying the side effects and best dose of everolimus when given with imatinib mesylate and to see how well they work in treating patients with locally advanced, locally recurrent or metastatic soft tissue sarcoma. Everolimus and imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: 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) SECONDARY OBJECTIVES: 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 study. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed synovial sarcoma that is platelet-derived growth factor receptor, alpha polypeptide positive (PDGFRA+)
- •Metastatic and/or locally advanced or locally recurrent disease
- •Patients must consent to tumor biopsies before therapy and after the second week of therapy
- •Patients who do not have accessible tumor for biopsy may be enrolled at the discretion of the principal investigator
- •Patients must have measurable disease, by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
- •Tumor lesions that are situated in a previously irradiated area may be considered measurable for the purposes of this study only if there is evidence of growth of the area following a course of irradiation that cannot be attributed to necrosis or bleeding into the tumor
- •Patients with brain metastasis that has been treated with definitive surgery or radiotherapy, and who have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids, are eligible for study
- •ECOG performance status 0-1
- •Life expectancy greater than 3 months
- •ANC ≥ 1,500/mm³
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (everolimus and imatinib mesylate)
Patients receive everolimus 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.
Intervention: diagnostic laboratory biomarker analysis
Treatment (everolimus and imatinib mesylate)
Patients receive everolimus 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.
Intervention: everolimus
Treatment (everolimus and imatinib mesylate)
Patients receive everolimus 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.
Intervention: imatinib mesylate
Outcomes
Primary Outcomes
Response Rate (CR + PR) Assessed by RECIST 1.1 (Phase II)
Time Frame: At 8 weeks