Clinical trial comparing the safety and efficacy of pimasertib and dacarbazine in previously untreated patients with locally advanced or metastatic malignant cutaneous melanoma showing the so-called N-Ras mutation.

Phase 1

Conditions: -RAS mutated locally advanced or metastatic malignant cutaneous melanoma
MedDRA version: 18.0Level: LLTClassification code 10025655Term: Malignant melanoma of skinSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002669-37-BE

Lead Sponsor: Merck Serono S.A. Geneva

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 184

Inclusion Criteria

1. Subjects with measurable, histologically or cytologically confirmed, unresectable locally advanced or metastatic cutaneous melanoma (stage III c or 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 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.
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, or 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 female
subjects or 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 157
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27

Exclusion Criteria

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 10^9/L, platelets < 100 x 10^9/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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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