metastatic or unresectable cutaneous melanoma MedDRA version: 21.1 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: MEK162
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: binimetinib
CAS Number: 606143-89-9
Current Sponsor code: MEK162
Other descriptive name: MEK162
Concentration unit: mg
Sponsors
Array BioPharma Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Diagnosis of locally advanced, unresectable or metastatic cutaneous or unknown primary melanoma (AJCC Stage IIIC or IV) (Uveal and mucosalmelnaoma are excluded) •Presence of NRAS Q61 mutation in tumor tissue prior to randomization •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 •Evidence of at least one measurable lesion as detected by radiological or photographic methods •Adequate bone marrow, organ function, cardiac and laboratory parameters •Normal functioning of daily living activities Other protocol defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 295 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 98
Exclusion criteria
Exclusion criteria: • Any untreated/non-stable brain lesion • Uveal or mucosal melanoma • History of or current evidence of retinal vein occlusion (RVO) • Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy. • Previous chemotherapy for unresectable locally advanced or metastatic melanoma. • History of Gilbert's syndrome • Prior therapy with a MEK- inhibitor • Impaired cardiovascular function or clinically significant cardiovascular diseases • Uncontrolled arterial hypertension despite medical treatment • HIV positive or active Hepatitis A or B • Impairment of gastrointestinal function or gastrointestinal disease • Patients with neuromuscular disorders that are associated with elevated CK. • Pregnant or nursing (lactating) women • Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study Other protocol defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with MEK162 prolongs PFS as compared to dacarbazine in patients with advanced unresectable, or metastatic NRAS mutation-positive cutaneous melanoma who are previously untreated or who have progressed on or after prior treatment with any number of lines of immunotherapy for unresectable or metastatic disease. ;Secondary Objective: Key secondary: To compare Overall Survival (OS) between treatment arms Other secondary: - To compare the Overall Response Rate (ORR) between treatment arms - To describe the time to objective response (TTR) in the two treatment arms - To describe the duration of objective response (DOR) between treatment arms - To compare the disease control rate (DCR) between treatment arms - To assess assess the safety and tolerability of MEK162 in this patient population using NCI CTCAE v4.03;Primary end point(s): Progression free survival (PFS) PFS is 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 by a Blinded Independent Review Committee (BIRC). The local Investigator's assessments will be used as supportive analyses.;Timepoint(s) of evaluation of this end point: The final PFS analysis is expected approximately 16 months after FPFV. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. Final analysis is expected to occur 21 m after FPFV 2. Approximately 16 months after the FPFV 3. Approximately 16 months after the FPFV 4. Approximately 16 months after the FPFV 5. Approximately 16 months after the FPFV 6. Approximately 16 months after the FPFV 7. Approximately 16 months after the FPFV 8. Approximately 16 months after the FPFV 9. Approximately 16 months after the FPFV 10. Approximately 16 months after the FPFV ;Secondary end point(s): 1. Overall Survival (OS) To compare OS between treatment arms. OS is calculated as the timefrom date of randomization to date of death due to any cause. 2. Overall Response Rate (ORR) ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately. 3. Time to Objective Response (TTR) TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response (PR). 4. Duration of objective response (DOR) DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer 5. Disease control rate (DCR) DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD) 6. Number of patients with adverse events To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), MUGA(Multi Gated Acquisition Scan)/echocardiogram and assessment of physical and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 7. Number of patients with serious adverse events To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, ECGs, MU | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactMargaret Vargo
Array BioPharma Inc.
Outcome results
None listed