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

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 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 prior first-line therapy (Ipilimumab-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:

MedlinePlus related topics: Cancer Melanoma Skin Cancer

Drug Information available for: Dacarbazine

U.S. FDA Resources

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 (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:	May 2016
Estimated Primary Completion Date:	October 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. Patients should be fasted 1 hour before and after the dose.
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 melanoma (AJCC Stage IIIC or IV)
Presence of NRAS Q61 mutation in tumor tissue prior to randomization
Naïve untreated patients or patients who have progressed on or after prior first-line 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 active/non-stable brain lesion
Non-cutaneous melanoma
History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease.

Patients with washout period < 12 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 or gastrointestinal disease
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

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

Contacts

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

Show 144 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

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 3, 2013
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) New Zealand: Food Safety Authority 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 Iceland: Icelandic Medicines Control Agency

Keywords provided by Novartis:

Melanoma
Cutaneous melanoma
Skin disease

Skin cancer
Skin Neoplasms
Neoplasm Metastasis

Additional relevant MeSH terms:

Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

Neoplasms by Site
Skin Diseases
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013