melanoma
Conditions
Interventions
MEK162 tablets of 15mg, Orally, continuous, daily
Startdose: 45mg / BID
or DTIC, 1000mg/m2 once every 3 weeks
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, unresectable or metastatic cutaneous or unknown primary melanoma AJCC Stage IIIC or IV (Uveal and mucosal melanoma are excluded) 3 Presence of NRAS Q61 mutation in tumor tissue prior to randomization, as determined by a central laboratory 4 Naïve untreated patients or patients who have progressed on or after prior treatment with any number of lines of immunotherapy for unresectable or metastatic melanoma; 5 Evidence of at least one measurable lesion as documented by radiological or photographic methods according to RECIST (version 1.1) 6 ECOG performance status of 0-1 7 Adequate bone marrow and organ function and laboratory parameters: * ANC * 1.5 x 109/L * Hemoglobin (Hgb) * 9 g/dL without transfusions * Platelets (PLT) * 100 x 109/L without transfusions * AST and/or ALT * 2.5 × upper limit of normal (ULN); patients with liver metastases * 5 ×ULN * Total bilirubin * 2 × ULN * Creatinine * 1.5 mg/dL 8 Adequate cardiac function: * left ventricular ejection fraction (LVEF) * 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram * QTc interval * 480 ms 9 Negative serum * HCG test (female patients of childbearing potential only) performed locally within 72 hrs prior to first dose
Exclusion criteria
Exclusion criteria: 1 Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression * 3 months. Patients must be off corticosteroid therapy for * 3 weeks. 2 Uveal or mucosal melanoma 3 History of leptomeningeal metastases 4 History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to RVO or CSR 5 History of allogeneic bone marrow transplantation or organ transplantation 6 History of Gilbert*s syndrome 7 Previous or concurrent malignancy with the following exceptions: * adequately treated basal cell or squamous cell carcinoma * in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to the study * a primary malignancy which has been completely resected and in complete remission for *5 years 8 Prior therapy with a MEK inhibitor 9 Patients with washout period
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| OS, calculated as the time from date of randomization to date of death due to any cause | — |
Primary
| Measure | Time frame |
|---|---|
| PFS, defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined based on tumor assessment (RECIST V1.1 criteria) as per BIRC and survival information. The local Investigator*s assessments will be used as supportive analyses. | — |
Countries
Netherlands
Outcome results
None listed