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

NCT01763164

Description:

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

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Study Comparing the Efficacy of MEK162 Versus <span class="go-doc-concept go-doc-intervention">Dacarbazine</span> in Unresectable or Metastatic <span class="go-doc-concept go-doc-biomarker">NRAS</span> <span class="go-doc-concept go-doc-keyword">Mutation</span>-positive <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01763164

    ORG ID: CMEK162A2301

    NCI ID: 2012-003593-51

    Trial Conditions

    Metastatic or Unresectable Cutaneous Melanoma

    Trial Interventions

    Drug Synonyms Arms
    MEK162 MEK162
    Dacarbazine Dacarbazine

    Trial Purpose

    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

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    MEK162 Experimental MEK162
    Dacarbazine Active Comparator Dacarbazine

    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

    - Nave 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression free survival (PFS)

    Secondary Outcome Measures

    Overall Survival (OS)

    Overall Response Rate (ORR)

    Time to Objective Response (TTR)

    Duration of objective response (DOR)

    Disease control rate (DCR)

    Number of patients with adverse events

    Number of patients with serious adverse events

    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)

    Change from baseline in the global health status score of the EORTC QLQ-C30

    Change from baseline in the EQ-5D-5L (EuroQol Group standardised instrument for use as a measure of health outcome)

    Trial Keywords

    Melanoma

    Cutaneous melanoma

    Skin disease

    Skin cancer

    Skin Neoplasms

    Neoplasm Metastasis