Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
  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


Condition Intervention Phase
Metastatic or Unresectable Cutaneous Melanoma
Drug: MEK162
Drug: Dacarbazine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 393
Study Start Date: July 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEK162 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.
Active Comparator: Dacarbazine 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763164

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 194 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01763164     History of Changes
Other Study ID Numbers: CMEK162A2301, 2012-003593-51
Study First Received: January 4, 2013
Last Updated: May 23, 2014
Health Authority: United States: Food and Drug Administration
Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Argentina: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Institutional Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Turkey: Ministry of Health
Brazil: Ministry of Health
Greece: Ministry of Health and Welfare

Keywords provided by Novartis:
Melanoma
Cutaneous melanoma
Skin disease
Skin cancer
Skin Neoplasms
Neoplasm Metastasis

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on November 23, 2014