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Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma

NCT01909453

Description:

This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized. Part 1: Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms: 1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm) 2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or 3. vemurafenib 960 mg BID (denoted as vemurafenib arm) Part 2: Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms: 1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or 2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Study Comparing Combination of <span class="go-doc-concept go-doc-intervention">LGX818</span> Plus MEK162 Versus Vemurafenib and <span class="go-doc-concept go-doc-intervention">LGX818</span> Monotherapy in <span class="go-doc-concept go-doc-biomarker">BRAF</span> <span class="go-doc-concept go-doc-keyword">Mutant</span> <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
  • Official Title: A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
  • Clinical Trial IDs

    NCT ID: NCT01909453

    ORG ID: CMEK162B2301

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    LGX818 LGX818 450mg+MEK162, LGX818 300mg+MEK162, LGX818
    MEK162 LGX818 450mg+MEK162, LGX818 300mg+MEK162
    vemurafenib Zelboraf, PLX4032, RO5185426 vemurafenib

    Trial Purpose

    This is 2-part, randomized, open label, multi-center, parallel group, phase III study
    comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818
    monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF
    V600 mutation. A total of approximately 900 patients will be randomized.

    Part 1:

    Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms:

    1. LGX818 450mg QD plus MEK162 45mg BID (denoted as Combo 450 arm)

    2. LGX818 300mg QD monotherapy (denoted as LGX818 arm) or

    3. vemurafenib 960mg BID (denoted as vemurafenib arm)

    Part 2:

    Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms:

    1. LGX818 300mg QD plus MEK162 45mg BID (denoted as Combo 300 arm) or

    2. LGX818 300mg QD monotherapy (denoted as LGX818 arm).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    LGX818 450mg+MEK162 Experimental LGX818 450 mg QD + MEK162 45mg BID LGX818, MEK162
    vemurafenib Active Comparator Vemurafenib 960mg BID vemurafenib
    LGX818 300mg+MEK162 Experimental LGX818 300 mg QD + MEK162 45mg BID LGX818, MEK162
    LGX818 Experimental LGX818 300 mg QD LGX818

    Eligibility Criteria

    Inclusion Criteria:

    - Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or
    unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV)

    - Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization

    - Nave untreated patients or patients who have progressed on or after prior first line
    immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant
    therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy
    or chemotherapy), except the administration of BRAF or MEK inhibitors

    - Evidence of at least one measurable lesion as detected by radiological or
    photographic methods

    - ECOG performance status of 0 or 1

    - Adequate bone marrow, organ function, cardiac and laboratory parameters

    - Normal functioning of daily living activities

    Exclusion Criteria:

    - Any untreated central nervous system (CNS) lesion

    - Uveal and mucosal melanoma

    - History of leptomeningeal metastases

    - History of or current evidence of central serous retinopathy (CSR), retinal vein
    occlusion (RVO) or history of retinal degenerative disease.

    - Any previous systemic chemotherapy treatment, extensive radiotherapy or
    investigational agent other than immunotherapy, or patients who have received more
    than one line of immunotherapy for locally advanced unresectable or metastatic
    melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at
    least 6 weeks prior to randomization

    - History of Gilbert's syndrome

    - Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor

    - Impaired cardiovascular function or clinically significant cardiovascular diseases

    - Uncontrolled arterial hypertension despite medical treatment

    - HIV positive or active Hepatitis B, and/or active Hepatitis C

    - Impairment of gastrointestinal function

    - 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)

    Progression Free Survival (PFS)

    Objective Response Rate (ORR)

    Time To Response (TTR)

    Disease Control Rate (DCR)

    Duration of objective response (DOR)

    Safety and tolerability of combination and LGX818

    ECOG Performance status (PS)

    Time to definitive 1 point deterioration in ECOG performance status

    Pharmacokinetics of LGX818 and MEK162

    Time to definitive 10% deteriortaion in global health status (EORTC QLQC30)

    Global health status (EORTC QLQC30)

    Time to definitive 10% deterioration in the FACT-M melanoma subscale

    Global health status (EQ-5D)

    Trial Keywords

    Melanoma

    Cutaneous melanoma

    Skin disease

    Skin cancer

    Skin Neoplasms

    Neoplasm Metastasis

    BRAF mutant

    BRAF V600E

    BRAF V600K

    Cancer

    LGX818

    MEK162

    vemurafenib

    combination

    BRAF inhibitor

    resistance

    The combination of a selective BRAF- and a MEK1/2-inhibitor

    Prior immunotherapy

    MEK inhibitor

    Phase III

    Combo 300, Combo 450