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


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Verified May 2017 by Memorial Sloan Kettering Cancer Center

Sponsor:

Collaborators:

Array BioPharma

Plexxikon

Information provided by (Responsible Party):

Memorial Sloan Kettering Cancer Center

ClinicalTrials.gov Identifier:

NCT03158103

First received: May 16, 2017

Last updated: May 16, 2017

Last verified: May 2017

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.

Gastrointestinal Stromal Tumor (GIST) Drug: MEK162
Drug: Pexidartinib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:

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

Masking: No masking
Primary Purpose: Treatment

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

Primary Outcome Measures:

Secondary Outcome Measures:

Estimated Enrollment: 40
Actual Study Start Date: April 15, 2017
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Experimental: 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.

Drug: MEK162

MEK162 at 30mg twice daily

Other Name: Binimetinib

Drug: Pexidartinib

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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.
  • 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
  • Patients who have neuromuscular disorders that are associated with elevated creatinine phosphokinase (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  • Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment;
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, ulcerative diseases, bowel resection with decreased intestinal absorption).
  • History of chronic inflammatory bowel disease or Crohn’s disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to randomization
  • Known history of acute or chronic pancreatitis
  • Prior therapy with a MEK inhibitor
  • Patients had a major surgery within 3 weeks prior to study entry or who have not recovered from side effects of such procedure
  • Women who are pregnant or lactating.
  • Sexually active males unless they use a condom during intercourse while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03158103

Contact: Ping Chi, MD, PhD 646-888-4166 chip@mskcc.org
Contact: William Tap, MD 646-888-4163

Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Contact: Ping Chi, MD    646-888-4166      
Contact: William Tap, MD    646-888-4163      
Principal Investigator: Ping Chi, MD, PhD         

Memorial Sloan Kettering Cancer Center

Array BioPharma

Plexxikon

Principal Investigator: Ping Chi, MD, PhD Memorial Sloan Kettering Cancer Center

Additional Information:

Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03158103     History of Changes
Other Study ID Numbers: 17-056
Study First Received: May 16, 2017
Last Updated: May 16, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:

MEK162 (Binimetinib)
Pexidartinib
17-056

Additional relevant MeSH terms:

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

ClinicalTrials.gov processed this record on May 17, 2017