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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01763164




Registration number
NCT01763164
Ethics application status
Date submitted
4/01/2013
Date registered
8/01/2013
Date last updated
22/03/2021

Titles & IDs
Public title
Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
Scientific title
The NEMO Trial (NRAS Melanoma and MEK Inhibitor):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
Secondary ID [1] 0 0
C4211002
Secondary ID [2] 0 0
CMEK162A2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic or Unresectable Cutaneous Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MEK162
Treatment: Drugs - Dacarbazine

Experimental: MEK162 -

Active Comparator: Dacarbazine -


Treatment: Drugs: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Timepoint [1] 0 0
From the date of randomization to the date of the first documented PD or death, whichever occurred first (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From the date of randomization to the date of death (maximum up to 107 weeks for binimetinib arm; maximum up to 88 weeks for dacarbazine arm)
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Secondary outcome [3] 0 0
Time to Response (TTR)
Timepoint [3] 0 0
From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Secondary outcome [4] 0 0
Duration of Objective Response (DOR)
Timepoint [4] 0 0
From the date of first documented response (CR or PR) to the first documented progression or death (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
From date of randomization until first documented response of CR, PR, SD or non-CR/non-PD (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Secondary outcome [6] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [6] 0 0
From baseline up to 219.4 weeks for binimetinib arm; From baseline up to 123.9 weeks for dacarbazine arm
Secondary outcome [7] 0 0
Number of Participants With Clinically Notable Hematology Shifts Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03
Timepoint [7] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [8] 0 0
Number of Participants With Clinically Notable Clinical Chemistry/Biochemistry Shifts Based on NCI-CTCAE Grade, Version 4.03
Timepoint [8] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [9] 0 0
Number of Participants With Clinically Notable Vital Signs
Timepoint [9] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [10] 0 0
Number of Participants With Notable Electrocardiogram (ECG) Values
Timepoint [10] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [11] 0 0
Number of Participants With Adverse Events of Special Interest: Cardiac Events
Timepoint [11] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [12] 0 0
Number of Participants With Clinically Significant Findings in Physical Examination
Timepoint [12] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [13] 0 0
Number of Participants With Adverse Events of Special Interest: Ocular Events
Timepoint [13] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [14] 0 0
Plasma Concentration of Binimetinib
Timepoint [14] 0 0
Day 1 of Week 1: Pre-dose, 1, 1.5, 2, 10 hours post-dose; Day 1 of Weeks 4, 7: Pre-dose, 1.5 hours post-dose; Day 1 of Weeks 10, 13: Pre-dose
Secondary outcome [15] 0 0
Time to Definitive 10% Deterioration in Global Health Status Score of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Timepoint [15] 0 0
From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Secondary outcome [16] 0 0
Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-Treatment Follow-up Visit 1, 2, 3, 4, 5 and 6
Timepoint [16] 0 0
Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57
Secondary outcome [17] 0 0
Change From Baseline in EuroQoL-5 Dimensions- 5 Levels (EQ-5D-5L) Index Score at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-treatment Follow-up Visit 1, 2, 3, 4, 5 and 6
Timepoint [17] 0 0
Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57
Secondary outcome [18] 0 0
Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Timepoint [18] 0 0
From baseline up to 73 weeks 3 days for binimetinib arm; From baseline up to 57 weeks 3 days for dacarbazine arm
Secondary outcome [19] 0 0
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Timepoint [19] 0 0
For both arms: Baseline, Weeks 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55 and 30-day Follow-up For binimetinib only: Weeks 58, 61, 64, 67, 70, 73
Secondary outcome [20] 0 0
Number of Participants With Neuroblastoma RAS Viral (V-ras) Oncogene Homolog (NRAS) Mutation Status at Baseline
Timepoint [20] 0 0
Baseline

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/06/2019
Sample size
Target
Accrual to date
Final
402
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse Hospital - Camperdown
Recruitment hospital [2] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [3] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
02290 - Gateshead
Recruitment postcode(s) [3] 0 0
2060 - North Sydney
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
05000 - Adelaide
Recruitment outside Australia
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Massachusetts
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Michigan
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Tennessee
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Texas
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Argentina
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Ciudad Autónoma DE Buenosaires
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Nürnberg
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Tübingen
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Ulm
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Roma
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Torino
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Netherlands
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Zwolle
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Mazowieckie
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Almada
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Porto
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Navarra
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La Coruna
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Madrid
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Sevilla
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Toledo
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Valencia
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Sweden
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Skane LAN
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Lund
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Switzerland
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Zürich (DE)
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Switzerland
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Genève
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Switzerland
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Lausanne
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Turkey
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Izmir
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Istanbul
Country [126] 0 0
United Kingdom
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Bristol, CITY OF
Country [127] 0 0
United Kingdom
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Cornwall
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United Kingdom
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EAST Sussex
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United Kingdom
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Essex
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United Kingdom
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Glamorgan
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United Kingdom
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Lancashire
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United Kingdom
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London, CITY OF
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United Kingdom
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Birmingham
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United Kingdom
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Leeds
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United Kingdom
State/province [135] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT01763164
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01763164