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

Phase 1

Active, not recruiting

• Conditions: on-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-kit; MedDRA version: 18.0Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: 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-HU
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-18
• Last Update Posted: 9 May 2016

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

1.Patient >18 years old, male or female, weighting more than 40 kg and BMI>18 kg/m²
2. 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. 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.measurable disease according to RECIST
5. ECOG = 2
6.life expectancy > 3 months
7. adequate organ function
• 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)
•Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
•Albuminaemia = 1 x LLN
•Urea = 2 x 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.Female patient of childbearing potential , who agrees to use two highly effective methods (1for the patient and 1 for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. Acceptable forms of contraception include:
•A documented placement of an IUD or IUS and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository)
•Documented tubal ligation (female sterilization). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used
•Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
•Any other contraceptive method with a documented failure rate of <1% per year
•Abstinence
Male patients must use medically acceptable methods of contraception if his female partner is pregnant, from the time of the first administration of the study drug until three months following administration of the last dose of study drug. Acceptable methods include:
• Condom;
•If you have undergone surgical sterilization (vasectomy with documentation of azoospermia) a condom should also be used.
Male patients must use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. The acceptable methods of contraception are as follows:
•Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
•Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);
•Your female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);
•Medically prescribed topica

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:
oAcute coronary syndrome
oAcute heart failure (class III or IV of the NYHA classification)
oSignificant 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