The purpose of this study is to evaluate the effects, good and/or bad, of MEK162 and imatinib
on the patient and on Gastrointestinal Stromal Tumor (GIST).
Funding Source - FDA OOPD, Array/Pfizer
- Patients must have pathologically confirmed GIST.
- In the Phase Ib portion, must have locally advanced or metastatic GIST and have
progressed on imatinib.
- In the Phase II portion, patients must be newly diagnosed or treatment naïve, or have
been off adjuvant imatinib therapy for at least 3 months. Patients with newly
diagnosed GIST and who had been on imatinib for up to 4 weeks prior to signing the
consent are allowed to enroll in order to expedite accrual.
- Patients must be at least 18 years of age.
- Disease must be measurable by RECIST 1.1.
- ECOG Performance Status 0 or 1.
- Adequate renal, hepatic, and hematologic function as the following: 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/mm3, Platelets ≥ 100,000/mm3, and hemoglobin ≥ 10g/dL.
- Patients of childbearing potential must have a negative serum pregnancy test within 14
days of treatment. Patients must agree to use a reliable barrier method of birth
control during and for 3 months following the last dose of study drug.
- Patient must have adequate cardiac function (left ventricular ejection fraction (LVEF)
≥50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; and QTc
- Patient must be able to take oral medications.
- Patients must sign an informed consent document.
- In the phase II portion of the study, patients that have been previously treated with
any systemic therapy for GIST are not permitted to enroll, with the exception of
adjuvant imatinib systemic therapy or exposure to imatinib within 4 weeks of signing
- Patients have a severe and/or uncontrolled medical disease (i.e., uncontrolled
diabetes, chronic renal disease, or active uncontrolled infection).
- Patients have known brain metastasis.
- Patients have known chronic liver disease (i.e., cirrhosis)
- Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C
- Other active malignancy (other than malignancies, which the investigator determines
are unlikely to interfere with treatment and safety analysis).
- 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
- History of retinal degenerative disease.
- History of Gilbert's syndrome.
- Patients have clinically significant cardiovascular disease, including any of the
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).
- Uncontrolled arterial hypertension despite appropriate medical therapy.
- Patients who have neuromuscular disorders that are associated with elevated creatinine
phosphokinase (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral
sclerosis, spinal muscular atrophy).
- Uncontrolled impairment of gastrointestinal function or gastrointestinal disease
(e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption
syndrome). Patients who have ulcerative colitis or other gastrointestinal diseases
that are well controlled are allowed to proceed with this study.
- 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 15 days 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.