A Phase I Study of Binimetinib in Combination With Pexidartinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

Memorial Sloan Kettering Cancer Center1 site in 1 country3 target enrollmentApril 15, 2017

Overview

Brief Summary

The purpose of this study is to test the safety and tolerability of the combination of pexidartinib and MEK162. This study tests different doses of pexidartinib in combination with different doses of MEK162 to see which dose combination of these drugs is safe and best tolerated in people.

Registry

clinicaltrials.gov

Start Date

April 15, 2017

End Date

April 28, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have pathologically confirmed GIST.
•In the Phase I dose escalation study, must have locally advanced, unresectable or metastatic GIST and have progressed on imatinib.
•In the dose expansion portion of the phase I study, patients must have locally advanced, unresectable or metastatic GIST that is resistant to imatinib. This population includes patients who have not been treated with imatinib (imatinib-naïve) but considered to have primary resistance to imatinib, i.e. KIT/PDGFRA wild-type GIST, and patients with imatinib-refractory disease, i.e. has had prior treatment with imatinib.
•Patients must be at least 18 years of age.
•Disease must be measurable by RECIST 1.
•ECOG Performance Status 0 or
•Patient must be able to take oral medications.
•Patients must sign an informed consent document.
•Adequate renal, hepatic, and hematologic function defined by:
•Serum Creatinine ≤ 1.5 mg/dL

Exclusion Criteria

•Patients have a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
•Patients have known active brain metastasis.
•Leptomeningeal disease
•Patients have known chronic liver disease (i.e., cirrhosis)
•Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus or known active or chronic infection with human immunodeficiency virus. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin \</= ULN) is allowed
•Known active tuberculosis
•Concurrent active inoperable locally advanced or metastatic malignancy (other than malignancies, which the investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced GIST).
•Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes).
•History of retinal degenerative disease.
•History of Gilbert's syndrome.

Arms & Interventions

MEK162 in combination with Pexidartinib

Pexidartinib will be administered orally by the patients on a twice daily basis throughout the treatment cycle. Pexidartinib is available in 200mg tablets. MEK162 wiIl be administered orally on a twice daily basis throughout the treatment cycle. MEK162 is available in 15mg tablets. In this phase I study all patients will have a 2-week lead in of pexidartinib therapy alone. Thereafter, pexidartinib will be administered in combination with MEK162 on a consecutive daily basis. A treatment cycle consists of 28 days. In the dose escalation portion the dose of pexidartinib and MEK 162 will depend on the dose level cohort onto which the patient is enrolled.

Intervention: MEK162

MEK162 in combination with Pexidartinib

Pexidartinib will be administered orally by the patients on a twice daily basis throughout the treatment cycle. Pexidartinib is available in 200mg tablets. MEK162 wiIl be administered orally on a twice daily basis throughout the treatment cycle. MEK162 is available in 15mg tablets. In this phase I study all patients will have a 2-week lead in of pexidartinib therapy alone. Thereafter, pexidartinib will be administered in combination with MEK162 on a consecutive daily basis. A treatment cycle consists of 28 days. In the dose escalation portion the dose of pexidartinib and MEK 162 will depend on the dose level cohort onto which the patient is enrolled.

Intervention: Pexidartinib