Linsitinib To Treat Patients With Gastrointestinal Stromal Tumors
RATIONALE: Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial studies how well linsitinib works in treating younger and adult patients with gastrointestinal stromal tumors.
Gastrointestinal Stromal Tumor
Genetic: nucleic acid sequencing
Genetic: reverse transcriptase-polymerase chain reaction
Genetic: western blotting
Other: enzyme-linked immunosorbent assay
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of OSI-906 in Patients With Pediatric and Adult Wild Type Gastrointestinal Stromal Tumors|
- Response rate (CR or PR) at 6 months [ Designated as safety issue: No ]
- Clinical benefit rate defined as SD ≥ 9 months [ Designated as safety issue: No ]
- Response duration, PFS, overall survival, and failure-free survival up to 37 weeks of treatment using Kaplan-Meier curves [ Designated as safety issue: No ]
- Adverse event profile of linsitinib on an ongoing basis [ Designated as safety issue: Yes ]
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
linsitinib 150 mg twice daily by mouth for 28 days per 28 day cycle
Other Name: OSI-906Genetic: nucleic acid sequencing Genetic: reverse transcriptase-polymerase chain reaction Genetic: western blotting Other: enzyme-linked immunosorbent assay Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Procedure: positron emission tomography Radiation: fludeoxyglucose F 18
- To determine the response rate (complete response [CR] and partial response [PR]) to treatment with linsitinib (OSI-906) in patients with advanced wild-type (WT) gastrointestinal stromal tumor (GIST) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- To determine the clinical benefit rate (stable disease [SD] ≥ 9 months, PR, or CR) in patients with advanced WT GIST treated with linsitinib.
- To determine the response duration, progression-free survival (PFS), and overall survival in patients with advanced WT GIST treated with linsitinib.
- To determine the tolerability and adverse event profile of linsitinib in patients with advanced GIST.
- To explore patterns of protein expression in serum and tumor tissues as predictors of response and PFS in advanced WT GIST treated with linsitinib.
- To evaluate the metabolic response to linsitinib using fludeoxyglucose F 18 (FDG)-positron emission tomography (PET).
- To determine if tumor metabolic response correlates with anatomic response and clinical benefit.
- To measure changes in tumor metabolism by FDG-PET qualitatively and semi-quantitatively with standard uptake value (SUV) and tumor body ratio (TBR) from baseline to first computed tomography (CT)-response evaluation and correlate the findings with size changes as defined by conventional cross-sectional imaging scans. (exploratory)
- To investigate correlations between glucose, insulin, and candidate tumor tissue and blood biomarkers with FDG-PET metabolic response. (exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to type of gastrointestinal stromal tumor (GIST): Pediatric wild-type (WT) GIST: diagnosed at a young age (< 18) or having characteristics consistent with Carney triad of Carney-Stretakis syndrome vs Adult WT GIST: all others.
Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during treatment for biomarker studies. Tumor tissue samples from biopsy or time of relapse may also be collected for correlative studies.
After completion of study treatment, patients are followed up for 30 days, every 12 weeks for 2 years (from date of first dose of linsitinib), and then annually thereafter.
|United States, California|
|Stanford Comprehensive Cancer Center|
|Stanford, California, United States, 94305|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 01225-6084|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109-0848|
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|United States, Pennsylvania|
|Fox Chase Cancer Center - Philadelphia|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|Principal Investigator:||Margaret von Mehren, MD||Fox Chase Cancer Center|