A multicentre, 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
- Conditions
- maligneSkin cancer10027476
- Registration Number
- NL-OMON41477
- Lead Sponsor
- Merck Serono S.A. Geneva
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Subjects with measurable, histologically or cytologically confirmed, unresectable locally advanced or metastatic cutaneous melanoma (M1a-c) 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.
2. Tumor lesions amenable to biopsy or available tumor tissue as archival samples.
3. Age >= 18 years.
4. Has read and understands 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.
5. 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, are surgically sterile.*
6. 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 for females subjects and female partners of male subjects is defined as follows: two barrier methods or one barrier method in combination with an intrauterine device or oral contraception.
1. Has previous systemic treatment for locally advanced or metastatic cutaneous melanoma (excluding adjuvant treatment).
2. Has non-measurable lesions, disease not evaluable by RECIST v. 1.1
3. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) >1.
4. Has bone marrow impairment as evidenced by Hemoglobin < 10.0 g/dL, Neutrophil count <1.5 x 109/L, platelets < 100 x 109/L.
5. Has renal impairment as evidenced by calculated creatinine clearance <60 mL/min (according to the Cockcroft-Gault formula).
6. Has liver function abnormality as defined by total bilirubin > 1.5 x ULN, or AST/ALT >2.5 x ULN, for subjects with liver involvement AST/ALT >5 x ULN.
7. Has significant cardiac conduction abnormalities, including QTc prolongation of >480 ms and/or pacemaker or clinically relevant impaired cardiovascular function (NYHA Class III/IV).
8. Has hypertension uncontrolled by medication
9. 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).
10. Has known active 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.
11. History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
12. Known HIV positivity, active hepatitis C, or active hepatitis B.
13. Has undergone surgical intervention within 28 days from Day 1 of trial drug treatment.
14. 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.
15. 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.
16. Has known hypersensitivity to dacarbazine.
17. Is a pregnant or nursing female.
18. Participated in another clinical trial within the past 28 days.
19. Has CPK level at baseline NCI CTCAE Grade >=2 (i.e., > 2.5 x ULN),
and/or has a previous history of myositis or rhabdomyolysis.
20. Is suitable for treatment with an approved B-Raf inhibitor or
antihuman
CTLA-4 (CD152) monoclonal antibodies (such as ipilimumab).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS, defined as the time from randomization to the first documentation of<br /><br>objective disease progression (according to RECIST v. 1.1) as determined by the<br /><br>investigator, or death, whichever comes first. Death will be considered as an<br /><br>event only if it is reported within 12 weeks after the last tumor assessment<br /><br>without progression.</p><br>
- Secondary Outcome Measures
Name Time Method