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

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ClinicalTrials.gov Identifier: NCT01763164
Recruitment Status : Active, not recruiting
First Posted : January 8, 2013
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Tracking Information
First Submitted Date  ICMJE January 4, 2013
First Posted Date  ICMJE January 8, 2013
Last Update Posted Date September 5, 2018
Study Start Date  ICMJE July 2013
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
Progression free survival (PFS) [ Time Frame: The final PFS analysis is expected approximately 26 months after FPFV. ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2013)
Progression freee survival (PFS) [ Time Frame: The final PFS analysis is expected approximately 16 months after FPFV. ]
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.
Change History Complete list of historical versions of study NCT01763164 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • Overall Survival (OS) [ Time Frame: Final analysis is expected to occur 31 months after FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    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 26 months after the FPFV ]
    To compare the global health status between the treatment.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2013)
  • Overall Survival (OS) [ Time Frame: Final analysis is expected to occur 21 months after FPFV ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    To compare the global health status between the treatment.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
Official Title  ICMJE 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
Brief 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic or Unresectable Cutaneous Melanoma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: MEK162
    Intervention: Drug: MEK162
  • Active Comparator: Dacarbazine
    Intervention: Drug: Dacarbazine
Publications * Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozón V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. doi: 10.1016/S1470-2045(17)30180-8. Epub 2017 Mar 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 13, 2016)
402
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2013)
393
Estimated Study Completion Date  ICMJE July 31, 2019
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Czechia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Portugal,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01763164
Other Study ID Numbers  ICMJE CMEK162A2301
2012-003593-51 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Array BioPharma
Study Sponsor  ICMJE Array BioPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Array BioPharma 303-381-6604
PRS Account Array BioPharma
Verification Date August 2018

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