A study to compare masitinib with dacarbazine in the treatment of patients with advanced melanoma carrying a mutation in a gene called c-kit

• Conditions: on-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-kit; MedDRA version: 16.0Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.0Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2009-017918-69-GR
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-08-27
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Patient >18 years old, male or female, weighting more than 40 kg or Body Mass Index (BMI)>18 kg/m²
2. Patient with histologically or cytologically confirmed non-resectable or metastatic stage 3 (non-resectable
IIIB or IIIC, AJCC TNM staging system 7th edition) or stage 4 melanoma
3. Patient with detectable c-kit JM mutation (mutation in exon 9, 11 or 13) confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma)
4. Patient with measurable disease according to RECIST
5. Patient with ECOG = 2
6. Patient with life expectancy > 3 months
7. Patient with adequate organ function
• Absolute neutrophils count (ANC) = 1.5 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PLT) = 75 x 109/L
• AST/ALT = 3 x ULN (= 5 x ULN in case of liver metastases)
• Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
• Bilirubin = 1.5 x ULN (= 3 x ULN in case of liver metastases)
• Creatine clearance = 50 mL/min (Cockcroft and Gault formula)
• Albuminaemia = 1 x LLN
• Urea = 2x ULN
• Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
8. Man or woman of child bearing potential, must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for six months after the last treatment intake. Female patients of childbearing potential must have a negative result in the regnancy test at screening and baseline.
9. Patient able and willing to comply with study visits and procedures as per protocol
10. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed.
11. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion Criteria

1. Pregnant, or nursing female patient

2. Patient with other malignancies from which the patient has been continuously disease-free for < 3 years, with the exception of melanoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer, ductal or lobular carcinoma in situ of the breast
3. Patient with active brain metastases are not eligible. Patients with treated brain metastases are eligible if : (a) presence of 3 brain lesions or less
(b) lesion(s) diameter is = 2 cm
(c) radiation therapy (gamma knife) was completed = 4 weeks prior to baseline
(d) surgery was completed =4 weeks prior to baseline
(e) lesions assessed by follow-up scan (or MRI if MRI performed before brain therapy) = 1 month after brain therapy are considered under control at baseline
4. Patient refractory to dacarbazine defined as patient presenting with disease progression within 3 months from the start of a previous dacarbazine therapy.
5. Prior treatment with a tyrosine kinase c-kit inhibitor
6. Patient with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrio- ventricular block 2 and 3, sino-atrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
7. Patient with clinically uncontrolled infectious diseases including HIV or AIDS-related illness
8. Major surgery or radiation therapy within four weeks of starting the study treatment
9. Patient with an history of poor compliance or an history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent

WASH-OUT

10. Previous radiotherapy, chemotherapy and/or previous adjuvant therapy with interferon, vaccines or therapy with IL-2 or GM-CSF within 4 weeks prior to baseline. Those patients will require a four weeks wash-out period before baseline. Similarly, any previous treatment with an investigational agent will require a wash - out period of four weeks before baseline

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified