malignant cutaneous melanoma skin cancer
Conditions
Interventions
MEK162 tablets 15mg
Orally, daily, continue
Startdosis: 45mg / twice daily or 60 mg / twice daily, depending on the arm
Sponsors
Array Biopharma
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female patients age >= 18 years 2. Histologically confirmed diagnosis of locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery 3. Must have documented presence of somatic BRAFV600 or NRAS mutation in tumor tissue 4. All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable central confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol 5. Evidence of measurable tumor disease as per RECIST 6. WHO performance status of 0-2 7. Adequate organ function and laboratory parameters: •ANC >= 1.5 x 109/L •Hemoglobin (Hgb) >= 10 g/dL •Platelets (PLT) >= 75 x 109/L •AST and/or ALT = 60 mL/min/1.73m2 8. LVEF >= 50% as determined by MUGA scan or TTE
Exclusion criteria
Exclusion criteria: 1. History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO 2. Patients with symptomatic CNS metastasis. 3. Prior therapy with a MEK- inhibitor 4. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: • History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) 140/100 mmHg 5. Known positive serology for HIV, active Hepatitis B, and/or active Hepatitis C infection 6. Any other condition that would, in the Investigator*s judgment, contraindicate patient*s participation in the clinical study due to safety concerns or compliance with clinical study procedures , e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc. 7. Patients who have received prior systemic anti-cancer treatment within the following time frames: •Patients who have received cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g., 6 weeks for nitrosourea, mitomycin-C) prior to starting study drugs •Patients who have received biologic therapy (e.g., antibodies) within 4 weeks prior to starting study drug •Patients who have been treated with continuous or intermittent small molecule therapeutics within
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| * To assess the effect of oral MEK162 on time-related efficacy parameters (progression free survival (PFS) and duration of response) * To characterize the safety and tolerability of oral MEK162 * To assess the effect of MEK162 on MEK/MAPK signaling, (PD changes of molecular status of ERK, DUSP6, MEK) in pre- vs. post-dose tumor biopsies * To characterize the baseline status of molecules relevant to MEK/MAPK signaling (PTEN, p53) in tumor tissue and potential correlation with clinical outcomes * To measure plasma concentrations of MEK162 and the pharmacologically active metabolite, AR00426032 | — |
Primary
| Measure | Time frame |
|---|---|
| To estimate the objective response rate (ORRs) of MEK162 in adult patients with advanced, unresectable, cutaneous malignant melanoma, i) harboring BARFV600 of ii) harboring NRAS mutations | — |
Countries
Netherlands
Outcome results
None listed