Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
Condition: Metastatic or Unresectable Cutaneous Melanoma
MeSH terms: Melanoma
Intervention: MEK162; Dacarbazine
Intervention description: 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.; 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.
Intervention MeSH terms: Dacarbazine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 402.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; Cutaneous melanoma; Skin disease; Skin cancer; Skin Neoplasms; Neoplasm Metastasis

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
    

Eligibility criteria:

        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