Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma

Status: Recruiting
Phase: Phase 3
Diagnosis: Cutaneous Skin Cancer
NCT ID: NCT01763164 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-138

 

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 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 prior first-line therapy (Ipilimumab-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

 

Conducting Institutions:
Massachusetts General Hospital, Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:
Keith Flaherty, MD, Massachusetts General Hospital

Site-responsible Investigators:
Frank Stephen Hodi, MD, Dana-Farber Cancer Institute

Contacts:
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Dana-Farber Cancer Institute: Suzanne MacRae, 617-632-5906, smacrae@partners.org

Eligibility Criteria

Inclusion Criteria: - Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma (AJCC Stage IIIC or IV) - Presence of NRAS Q61 mutation in tumor tissue prior to randomization - Naïve untreated patients or patients who have progressed on or after prior first-line 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 active/non-stable brain lesion - Non-cutaneous melanoma - History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease. Patients with washout period < 12 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 inclusion/exclusion criteria may apply
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