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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01763164
First received: January 4, 2013
Last updated: May 23, 2014
Last verified: May 2014

January 4, 2013
May 23, 2014
July 2013
December 2014   (final data collection date for primary outcome measure)
Progression free survival (PFS) [ Time Frame: The final PFS analysis is expected approximately 16 months after FPFV. ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined by a Blinded Independent Review Committee (BIRC). The local Investigator's assessments will be used as supportive analyses.
Progression freee survival (PFS) [ Time Frame: The final PFS analysis is expected approximately 16 months after FPFV. ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined by a Blinded Independent Review Committee (BIRC). The local Investigator's assessments will be used as supportive analyses.
Complete list of historical versions of study NCT01763164 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: Final analysis is expected to occur 21 months after FPFV ] [ Designated as safety issue: No ]
    To compare OS between treatment arms. OS is calculated as the time from date of randomization to date of death due to any cause.
  • Overall Response Rate (ORR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately.
  • Time to Objective Response (TTR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response(PR).
  • Duration of objective response (DOR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer
  • Disease control rate (DCR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD)
  • Number of patients with adverse events [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), MUGA(Multi Gated Acquisition Scan)/echocardiogram and assessment of physical and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03
  • Number of patients with serious adverse events [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, ECGs, MUGA/echocardiogram and assessment of physical and ocular examinations graded according to the NCI CTCAE v4.03
  • 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) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatments.
  • Change from baseline in the global health status score of the EORTC QLQ-C30 [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.
  • Change from baseline in the EQ-5D-5L (EuroQol Group standardised instrument for use as a measure of health outcome) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.
  • Overall Survival (OS) [ Time Frame: Final analysis is expected to occur 21 months after FPFV ] [ Designated as safety issue: No ]
    To compare OS between treatment arms. OS is calculated as the time from date of randomization to date of death due to any cause.
  • Overall Response Rate (ORR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately.
  • Time to Objective Response (TTR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response(PR).
  • Duration of objective response (DOR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer
  • Disease control rate (DCR) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD)
  • Number of patients with adverse events [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), MUGA(Multi Gated Acquisition Scan)/echocardiogram and assessment of physical and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03
  • Number of patients with serious adverse events [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, ECGs, MUGA/echocardiogram and assessment of physical and ocular examinations graded according to the NCI CTCAE v4.03
  • 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) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatments.
  • Change from baseline in the global health status score of the EORTC QLQ-C30 [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.
  • Change from baseline in the EQ-5D (EuroQol Group standardised instrument for use as a measure of health outcome) [ Time Frame: Approximately 16 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.
Not Provided
Not Provided
 
Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
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

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

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic or Unresectable Cutaneous Melanoma
  • Drug: MEK162
    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.
  • Drug: Dacarbazine
    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.
  • Experimental: MEK162
    Intervention: Drug: MEK162
  • Active Comparator: Dacarbazine
    Intervention: Drug: Dacarbazine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
393
July 2016
December 2014   (final data collection date for primary outcome measure)

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 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

Both
18 Years and older
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Germany,   Spain,   United Kingdom,   Turkey,   Switzerland,   Sweden,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Czech Republic,   France,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Russian Federation,   Slovakia,   South Africa
 
NCT01763164
CMEK162A2301, 2012-003593-51
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP