N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous MelanomaPhase 2NCT01693068
Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma
A Phase 2 study testing Pimasertib and Dacarbazine in people with N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma, run by EMD Serono at 101 sites in 14 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma
- What is being tested?
- Pimasertib and Dacarbazine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 101 sitesin 14 countries
- Study dates
- 5 Dec 2012to 24 Oct 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with measurable, histologically or cytologically confirmed, locally advanced or metastatic cutaneous melanoma (stage III c or M1ac) N-Ras mutated. If N-Ras mutational status is unknown at screening, it must be prospectively defined before inclusion. If N-Ras mutational status is already known before screening, it must be retrospectively confirmed after inclusion by the sponsor.
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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.
- Has known hypersensitivity to dacarbazine.
- Is a pregnant or nursing female.
- Participated in another clinical trial within the past 28 days.
- Has creatine phosphokinase (CPK) level at baseline National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=2 (i.e > 2.5 * ULN), and/or has a previous history of myositis or rhabdomyolysis.
- Is suitable for treatment with an approved B-Raf inhibitor (exclusion criteria implemented in German amendment only).
Trial locations and contacts
101 sites in 14 countries.
101 sites in 14 countries
Germany20 sites
Research Site
Augsburg
Research Site
Berlin
Research Site
Bonn
Research Site
Buxtehude
Research Site
Cologne
Research site
Düsseldorf
Research Site
Erlangen
Research Site
Essen
Research Site
Frankfurt am Main
Research Site
Hamburg
Research Site
Hanover
Research Site
Kiel
Research Site
Leipzig
Research Site
Magdeburg
Research Site
Mainz
Research site
München
Research Site
Münster
Research Site
Plauen
Research Site
Tübingen
Research Site
Würzburg
United States15 sites
Research Site
Birmingham, Alabama
Research Site
Boston, Massachusetts
Research Site
Columbus, Ohio
Research Site
Dallas, Texas
Research Site
Indianapolis, Indiana
Research Site
Madison, Wisconsin
Research Site
Maywood, Illinois
Research Site
Miami Beach, Florida
Research Site
Morristown, New Jersey
Research Site
New York, New York
Research Site
Orlando, Florida
Please contact the US Medical Information in
Rockland, Massachusetts
Research Site
San Francisco, California
Research Site
St Louis, Missouri
Research Site
Tucson, Arizona
France13 sites
Research Site
Bordeaux
Research Site
Brest
Research Site
Dijon
Research Site
Lille
Research Site
Lyon
Research Site
Marseille
Research Site
Montpellier
Research Site
Nantes
Research Site
Paris
Research Site
Pierre-Bénite
Research Site
Rennes
Research Site
Toulouse
Research Site
Villejuif
Australia12 sites
Research Site
Adelaide, SA
Research Site
Albury/Wodonga
Research Site
Auchenflower
Research Site
Box Hill
Research Site
Greenslopes
Research Site
Herston
Research Site
Malvern
Research Site
North Sydney
Research Site
Prahran
Research Site
Wendouree
Research Site
Woodville South
Research site
Woolloongabba
Italy8 sites
Research Site
Bari
Research Site
Genova
Research Site
Meldola - FC
Research Site
Milan
Research Site
Naples
Research Site
Padova
Research Site
Roma
Research Site
Siena
Spain8 sites
Research Site
Badalona
Research Site
Barcelona
Research Site
L'Hospitalet de Llobregat
Research Site
Madrid
Research Site
Majadahonda
Research Site
Málaga
Research Site
Pamplona
Research Site
Seville
United Kingdom5 sites
Research Site
Cambridge
Research Site
London
Research Site
Manchester
Research Site
Newcastle upon Tyne
Research Site
Southampton
New Zealand4 sites
Research Site
Christchurch
Research Site
Hamilton
Research Site
Palmerston North
Research Site
Tauranga
South Africa4 sites
Research Site
Durban
Research Site
Johannesburg
Research Site
Pietermaritzburg
Research Site
Pretoria
Israel3 sites
Research Site
Jerusalem
Research Site
Ramat Gan
Research Site
Tel Aviv
Netherlands3 sites
Research Site
Groningen
Research Site
Rotterdam
Research Site
Utrecht
About this study
Official title: 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
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.
- Being tested
- Pimasertib, Dacarbazine
- Keywords
- Cutaneous Melanoma, Dacarbazine, Pimasertib, N-Ras
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PimasertibDrug
Also called MSC1936369B, AS703026
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.
DacarbazineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Pimasertib | Experimental | Not described Receives: Drug: Pimasertib |
| Dacarbazine | Active comparator | Not described Receives: Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
ORR was defined as the percentage of subjects with complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters along with absence of new lesions and disease progression in non-target lesions.
Measured: 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)
DCR was defined as the percentage of subjects with CR, PR, or stable disease (SD) for greater than (>) 3 months assessed by investigator according to RECIST version 1.1. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than <10 mm. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters along with absence of new lesions and disease progression in non-target lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: 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
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, 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. Percentage of Subjects with PFS at 6 Months were reported.
Measured: 6 months
Overall Survival (OS)
OS was defined as the time (in months) from randomization to death due to any cause. Subjects without a death date were to be censored at the minimum of last known date alive, defined as the latest date available on the electronic case report form, and cut-off date.
Measured: 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
OS was defined as the time (in months) from randomization to death due to any cause. Subjects without a death date were to be censored at the minimum of last known date alive, defined as the latest date available on the electronic case report form, and cut-off date. Percentage of Subjects with OS at 12 months were reported.
Measured: 12 months
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M TS) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
QoL assessed using Function Assessment Cancer Therapy-melanoma (FACT-M) assessment tool. This includes 27-item FACT-General (FACT-G) questionnaire which consists of 24 questions;7 relating to physical well-being (PWB),7 relating to social/family well-being (SWB),6 relating to emotional well-being (EWB) and 7 relating to functional well-being (FWB). Also, it includes melanoma-specific subscale consists of 16 questions for Melanoma Subscale (MS) and 8 questions for Melanoma Surgery Scale (MSS).Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life.
Measured: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Trial Outcome Index (FACT-M TOI) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
QoL assessed using FACT-M assessment tool. This includes 27-item FACT-G questionnaire which consists of 24 questions; 7 relating to PWB, 7 relating to SWB, 6 relating to EWB and 7 relating to FWB. Also, it includes melanoma-specific subscale consists of 16 questions for MS and 8 questions for the MSS. Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Trial Outcome Index (FACT-M TOI) ranges from 0 to a high of 120 and is derived as: FACT-M TOI = PWB Score + FWB Score +MS Score. Higher scores represent a better quality of life.
Measured: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 33 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs. TEAEs were to be reported separately for dacarbazine, pimasertib and pimasertib (crossover) reporting arms.
Measured: Baseline up to cut-off date (04-Jul-2015)
Number of Subjects With Adverse Events (AEs) of Special Interest
Adverse events of special interest included ocular retinal vein occlusion, serious retinal detachment or similar retinal abnormality characterized by accumulation of serous fluid in the retina, creatine phosphokinase (CPK) elevation and isoenzyme TEAE of Special Interest (Grade >=2) and acute renal failure (Grade >=2). Subjects were presented under 3 reporting groups: Dacarbazine group: for subjects who received at least 1 dose of dacarbazine; Pimasertib group: for subjects who received at least 1 dose of pimasertib; Pimasertib (Crossover) group: for subjects who were initially randomized and received dacarbazine, but crossed over to pimasertib treatment on progression of their disease.
Measured: Baseline up to cut-off date (04-Jul-2015)
Number of Subjects With Clinically Significant Change From Baseline in Laboratory Parameter, Vital Signs, Electrocardiogram (ECG) and Ophthalmologic Findings
Subjects were presented under 3 reporting groups: Dacarbazine group: for subjects who received at least 1 dose of dacarbazine; Pimasertib group: for subjects who received at least 1 dose of pimasertib; Pimasertib (Crossover) group: for subjects who were initially randomized and received dacarbazine, but crossed over to pimasertib treatment on progression of their disease.
Measured: Baseline up to cut-off date (04-Jul-2015)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2012 (estimated)
- Study start5 Dec 2012
- Primary completion4 Jul 2015
- Study completion24 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01693068
- Sponsor's protocol ID
- EMR 200066-007
- Other IDs
- 2012-002669-37
- Status last verified
- Dec 2017
- First submitted
- 14 Sep 2012
- Last updated
- 5 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 32610581
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01693068
- Acronym / sponsor ID
- EMR 200066-007
- Keywords
- Cutaneous Melanoma, Dacarbazine, Pimasertib, N-Ras
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 5 Dec 2012 (actual)
- Primary completion
- 4 Jul 2015 (actual)
- Study completion
- 24 Oct 2016 (actual)
- First posted
- 26 Sep 2012 (estimated)
- Results
- Posted 5 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pimasertib | Experimental | Drug: Pimasertib |
| Dacarbazine | Active comparator | Drug: Dacarbazine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects with measurable, histologically or cytologically confirmed, locally advanced or metastatic cutaneous melanoma (stage III c or M1ac) N-Ras mutated. If N-Ras mutational status is unknown at screening, it must be prospectively defined before inclusion. If N-Ras mutational status is already known before screening, it must be retrospectively confirmed after inclusion by the sponsor.
- 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".
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PimasertibAlso: MSC1936369B, AS703026Subjects 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. | Drug | Pimasertib |
| DacarbazineSubjects 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. | Drug | Dacarbazine |
Primary outcome
Progression Free Survival (PFS)
Time frame: 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)
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.
10 secondary outcomes
Objective Response Rate (ORR)
Time frame: 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)
Time frame: 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
Time frame: 6 months
Overall Survival (OS)
Time frame: 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
Time frame: 12 months
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M TS) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Trial Outcome Index (FACT-M TOI) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
Time frame: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
Time frame: Baseline up to cut-off date (04-Jul-2015)
Number of Subjects With Adverse Events (AEs) of Special Interest
Time frame: Baseline up to cut-off date (04-Jul-2015)
Number of Subjects With Clinically Significant Change From Baseline in Laboratory Parameter, Vital Signs, Electrocardiogram (ECG) and Ophthalmologic Findings
Time frame: Baseline up to cut-off date (04-Jul-2015)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32610581Lebbe 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
101 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pimasertib and Dacarbazine in people with N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma, run by EMD Serono at 101 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 101 sites in Germany, United States, France, Australia, Italy and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01693068, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2018.