Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma
A Multicenter, Open Label, Randomized Phase II Trial of the MEK Inhibitor Pimasertib or Dacarbazine in Previously Untreated Subjects With N-Ras Mutated Locally Advanced or Metastatic Malignant Cutaneous Melanoma
2 other identifiers
interventional
194
14 countries
101
Brief Summary
This is a Phase 2, multicenter, randomized, controlled, open-label trial of pimasertib versus dacarbazine aimed to confirm the activity of pimasertib in previously untreated subjects with N-Ras mutated locally advanced or metastatic malignant cutaneous melanoma by comparing the progression-free survival (PFS) of subjects treated with either pimasertib or dacarbazine and by getting a better understanding of the efficacy, safety, pharmacogenomics (PGx) and their relationship with pimasertib exposure.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Dec 2012
Typical duration for phase_2
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 14, 2012
CompletedFirst Posted
Study publicly available on registry
September 26, 2012
CompletedStudy Start
First participant enrolled
December 5, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 4, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
October 24, 2016
CompletedResults Posted
Study results publicly available
January 5, 2018
CompletedJanuary 5, 2018
December 1, 2017
2.6 years
September 14, 2012
October 23, 2017
December 5, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS was defined as the duration (in weeks) from randomization until the first progressive disease (PD) observation as assessed by the Investigator according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1, or death due to any cause when death occurred within 12 weeks after the last tumor assessment (otherwise censored), whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Secondary Outcomes (10)
Objective Response Rate (ORR)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Disease Control Rate (DCR)
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Percentage of Subjects With Progression-free Survival (PFS) at 6 Months
6 months
Overall Survival (OS)
From date of randomization until date of death from any cause, assessed up to cut-off date (04-Jul-2015)
Percentage of Subjects With Overall Survival (OS) at 12 Months
12 months
- +5 more secondary outcomes
Study Arms (2)
Pimasertib
EXPERIMENTALDacarbazine
ACTIVE COMPARATORInterventions
Subjects will receive pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment will consist of repeated 21-day cycles which will continue until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first.
Subjects will receive dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m\^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. Eligible subjects with documented tumor progression on dacarbazine will offer to switch to pimasertib treatment.
Eligibility Criteria
You may qualify if:
- Tumor lesions amenable to biopsy or available tumor tissue as archival samples.
- Age greater than or equal to (\>=) 18 years.
- Has read and understood the informed consent form and is willing and able to give informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments.
- Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years, or are surgically sterile".
- Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose of trial medication. Effective contraception is defined as the method of contraception with a failure rate of less than 1% per year. Adequate contraception is defined as follows: two barrier methods or one barrier method with a spermicidal or intrauterine device or oral contraception for female partners of male subjects.
You may not qualify if:
- Has previous systemic treatment for locally advanced or metastatic cutaneous melanoma (excluding adjuvant treatment).
- Has non-measurable lesions, disease not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
- Has an Eastern Cooperative Oncology Group performance status (ECOG PS) \>1.
- Has bone marrow impairment as evidenced by Hemoglobin \<10.0 g/dL, Neutrophil count \<1.5 \* 10\^9/L, platelets \<100 \* 10\^9/L.
- Has renal impairment as evidenced by calculated creatinine clearance \<60 mL/min (according to the Cockcroft-Gault formula).
- Has liver function abnormality as defined by total bilirubin \>1.5 \* Upper Limit of Normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>2.5 \* ULN, for subjects with liver involvement AST/ALT \>5 \* ULN.
- Has significant cardiac conduction abnormalities, including QTc prolongation of \>480 milliseconds and/or pacemaker or clinically relevant impaired cardiovascular function.
- Has hypertension uncontrolled by medication
- Has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for RVO (e.g., uncontrolled glaucoma or ocular hypertension).
- Has known active central nervous system (CNS) metastases unless previously radiotherapy treated, stable by CT scan for at least 3 months without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants.
- History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
- Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B.
- Has undergone surgical intervention within 28 days from Day 1 of trial drug treatment.
- Has received extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from Day 1 of trial drug treatment.
- Has history of any other significant medical disease such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion or has a psychiatric condition that might impair the subject well-being or preclude full participation in the trial.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- EMD Seronolead
- Merck KGaA, Darmstadt, Germanycollaborator
Study Sites (101)
Research Site
Birmingham, Alabama, United States
Research Site
Tucson, Arizona, United States
Research Site
San Francisco, California, United States
Research Site
Miami Beach, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Maywood, Illinois, United States
Research Site
Indianapolis, Indiana, United States
Research Site
Boston, Massachusetts, United States
Please contact the US Medical Information in
Rockland, Massachusetts, United States
Research Site
St Louis, Missouri, United States
Research Site
Morristown, New Jersey, United States
Research Site
New York, New York, United States
Research Site
Columbus, Ohio, United States
Research Site
Dallas, Texas, United States
Research Site
Madison, Wisconsin, United States
Research Site
Adelaide, SA, Australia
Research Site
Albury/Wodonga, Australia
Research Site
Auchenflower, Australia
Research Site
Box Hill, Australia
Research Site
Greenslopes, Australia
Research Site
Herston, Australia
Research Site
Malvern, Australia
Research Site
North Sydney, Australia
Research Site
Prahran, Australia
Research Site
Wendouree, Australia
Research Site
Woodville South, Australia
Research site
Woolloongabba, Australia
Research Site
Brussels, Belgium
Research Site
Edegem, Belgium
Research Site
Bordeaux, France
Research Site
Brest, France
Research Site
Dijon, France
Research Site
Lille, France
Research Site
Lyon, France
Research Site
Marseille, France
Research Site
Montpellier, France
Research Site
Nantes, France
Research Site
Paris, France
Research Site
Pierre-Bénite, France
Research Site
Rennes, France
Research Site
Toulouse, France
Research Site
Villejuif, France
Research Site
Augsburg, Germany
Research Site
Berlin, Germany
Research Site
Bonn, Germany
Research Site
Buxtehude, Germany
Research Site
Cologne, Germany
Research site
Düsseldorf, Germany
Research Site
Erlangen, Germany
Research Site
Essen, Germany
Research Site
Frankfurt am Main, Germany
Research Site
Hamburg, Germany
Research Site
Hanover, Germany
Research Site
Kiel, Germany
Research Site
Leipzig, Germany
Research Site
Magdeburg, Germany
Research Site
Mainz, Germany
Research site
München, Germany
Research Site
Münster, Germany
Research Site
Plauen, Germany
Research Site
Tübingen, Germany
Research Site
Würzburg, Germany
Research Site
Jerusalem, Israel
Research Site
Ramat Gan, Israel
Research Site
Tel Aviv, Israel
Research Site
Bari, Italy
Research Site
Genova, Italy
Research Site
Meldola - FC, Italy
Research Site
Milan, Italy
Research Site
Napoli, Italy
Research Site
Padua, Italy
Research Site
Roma, Italy
Research Site
Siena, Italy
Research Site
Groningen, Netherlands
Research Site
Rotterdam, Netherlands
Research Site
Utrecht, Netherlands
Research Site
Christchurch, New Zealand
Research Site
Hamilton, New Zealand
Research Site
Palmerston North, New Zealand
Research Site
Tauranga, New Zealand
Research Site
Durban, South Africa
Research Site
Johannesburg, South Africa
Research Site
Pietermaritzburg, South Africa
Research Site
Pretoria, South Africa
Research Site
Badalona, Spain
Research Site
Barcelona, Spain
Research Site
L'Hospitalet de Llobregat, Spain
Research Site
Madrid, Spain
Research Site
Majadahonda, Spain
Research Site
Málaga, Spain
Research Site
Pamplona, Spain
Research Site
Seville, Spain
Research Site
Gothenburg, Sweden
Research Site
Stockholm, Sweden
Research Site
Basel, Switzerland
Research Site
Zurich, Switzerland
Research Site
Cambridge, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Newcastle upon Tyne, United Kingdom
Research Site
Southampton, United Kingdom
Related Publications (1)
Lebbe C, Dutriaux C, Lesimple T, Kruit W, Kerger J, Thomas L, Guillot B, Braud F, Garbe C, Grob JJ, Loquai C, Ferraresi V, Robert C, Vasey P, Conry R, Isaacs R, Espinosa E, Schueler A, Massimini G, Dreno B. Pimasertib Versus Dacarbazine in Patients With Unresectable NRAS-Mutated Cutaneous Melanoma: Phase II, Randomized, Controlled Trial with Crossover. Cancers (Basel). 2020 Jun 29;12(7):1727. doi: 10.3390/cancers12071727.
PMID: 32610581DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Merck KGaA Communication Center
- Organization
- Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Study Director
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2012
First Posted
September 26, 2012
Study Start
December 5, 2012
Primary Completion
July 4, 2015
Study Completion
October 24, 2016
Last Updated
January 5, 2018
Results First Posted
January 5, 2018
Record last verified: 2017-12