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

Pfizer

Status and phase

Completed

Phase 3

Conditions

Metastatic or Unresectable Cutaneous Melanoma

Treatments

Drug: MEK162

Drug: Dacarbazine

Study type

Interventional

Funder types

Industry

Identifiers

NCT01763164

C4211002 (Other Identifier)

CMEK162A2301

2012-003593-51 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment

402 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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