A Study of MEK162 (Binimetinib) in Combination With Pexidartinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

NCT03158103 | Completed Phase 1 FDA Drug

• 1 other identifier: 17-056
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastrointestinal Stromal Tumor (GIST)

Keywords

MEK162 (Binimetinib); Pexidartinib; 17-056

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RP2D)

  The dose escalation study will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.

  1 year

Secondary Outcomes (2)

• Number of participants with complete response

  within 32 weeks

• Number of participants with partial response

  within 32 weeks

Study Arms (1)

MEK162 in combination with Pexidartinib

EXPERIMENTAL

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.

Drug: MEK162; Drug: Pexidartinib

Interventions

MEK162 DRUG

MEK162 at 30mg twice daily

Also known as: Binimetinib

MEK162 in combination with Pexidartinib

Pexidartinib DRUG

pexidartinib 600mg daily (400mg in the morning, 200mg at night) for 4 weeks (1 cycle)

MEK162 in combination with Pexidartinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1.
• ECOG Performance Status 0 or 1.
• 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
• Total Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Serum AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor)
• ANC ≥ 1500/mm\^3
• Platelets ≥ 100,000/mm\^3
• Hemoglobin ≥ 9g/dL

You may not qualify if:

• 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.
• Patients have clinically significant cardiovascular disease, including any of the following: 1) History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting \< 6 months prior to screening; 2) symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV); 3) evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities \< 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT).
• A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women).
• Left ventricular ejection fraction (LVEF) \<50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
• Uncontrolled arterial hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100mmHg despite current therapy.
• History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Array BioPharma: collaborator
• Plexxikon: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Rosenbaum E, Kelly C, D'Angelo SP, Dickson MA, Gounder M, Keohan ML, Movva S, Condy M, Adamson T, Mcfadyen CR, Antonescu CR, Hwang S, Singer S, Qin LX, Tap WD, Chi P. A Phase I Study of Binimetinib (MEK162) Combined with Pexidartinib (PLX3397) in Patients with Advanced Gastrointestinal Stromal Tumor. Oncologist. 2019 Oct;24(10):1309-e983. doi: 10.1634/theoncologist.2019-0418. Epub 2019 Jun 18.

  PMID: 31213500 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

binimetinib; pexidartinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Ping Chi, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The phase I study consists of a dose-escalation cohort and a dose-expansion cohort.

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 17, 2017
• Study Start: April 15, 2017
• Primary Completion: April 28, 2021
• Study Completion: April 28, 2021
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

US (1)