Overview

This trial is active, not recruiting.

Condition metastatic or unresectable cutaneous melanoma
Treatments mek162, dacarbazine
Phase phase 3
Targets MEK, NRAS
Sponsor Array BioPharma
Start date July 2013
End date December 2015
Trial size 402 participants
Trial identifier NCT01763164, 2012-003593-51, CMEK162A2301

Summary

Two-arm, randomized, prospective, open-label, multi-center, phase III study to compare the efficacy and safety of MEK162 (45 mg BID) versus dacarbazine (1000 mg/m2 IV every 3 weeks) in patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) NRAS Q61 mutation-positive cutaneous or unknown primary melanoma. The mutation analysis will be performed at a central laboratory. Only those patients with Q61 mutation per central laboratory and meet all eligibility criteria will be randomized. A total of 393 patients will be randomized 2:1 to receive either MEK162 or dacarbazine. Patients will be stratified according to AJCC stage (IIIC, IVM1a, and IVM1b versus IVM1c), ECOG Performance status (0 versus 1) and any prior number of lines of immunotherapy (immunotherapies versus none). This study will use an Interactive Response Technology (IRT). The primary end point of the study is progression-free survival. Key secondary end point is overall survival

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
mek162
MEK162 will be administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food.
(Active Comparator)
dacarbazine
Patients randomized to dacarbazine will receive an IV infusion of dacarbazine 1000 mg/m2 over the course of 1 hour on day 1 and then every three weeks.

Primary Outcomes

Measure
Progression free survival (PFS)
time frame: The final PFS analysis is expected approximately 26 months after FPFV.

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Final analysis is expected to occur 31 months after FPFV
Overall Response Rate (ORR)
time frame: Approximately 26 months after the FPFV
Time to Objective Response (TTR)
time frame: Approximately 26 months after the FPFV
Duration of objective response (DOR)
time frame: Approximately 26 months after the FPFV
Disease control rate (DCR)
time frame: Approximately 26 months after the FPFV
Number of patients with adverse events
time frame: Approximately 26 months after the FPFV
Number of patients with serious adverse events
time frame: Approximately 26 months after the FPFV
Time to definitive 10% deterioration in the global health status score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)
time frame: Approximately 26 months after the FPFV
Change from baseline in the global health status score of the EORTC QLQ-C30
time frame: Approximately 26 months after the FPFV
Change from baseline in the EQ-5D-5L (EuroQol Group standardised instrument for use as a measure of health outcome)
time frame: Approximately 26 months after the FPFV

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Diagnosis of locally advanced, unresectable or metastatic cutaneous or melanoma of unknown primary AJCC Stage IIIC or IV (uveal and mucosal melanoma are excluded) - Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory - Naïve untreated patients or patients who have progressed on or after any number of prior lines of immunotherapy for unresectable locally advanced 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 Exclusion Criteria: - Any untreated CNS metastases - Uveal or mucosal melanoma - History of or current evidence of retinal vein occlusion (RVO) or risk factors of RVO - Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy. - Previous systemic 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 - Patients who have undergone major surgery or radiotherapy ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure; - 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 inclusion/exclusion criteria may apply

Additional Information

Official title A Randomized Phase III, Open Label, Multicenter, Two-arm Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Patients With Advanced Unresectable or Metastatic NRAS Mutation-positive Melanoma
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Array BioPharma.