A prospective, multicenter, randomized, open-label, active-controlled, two-parallel groups, phase 3 study to compare the efficacy and safety of masitinib at 7.5 mg/kg/day to dacarbazine in the treatment of patients with non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-kit - Not applicable

Phase 1

• Conditions: Patients with non-resectable or metastatic stage 3 or stage 4 melanoma carrying a mutation in the juxta membrane domain of c-kit; MedDRA version: 19.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.1Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-16
• Last Update Posted: 23 January 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 78

Inclusion Criteria

1. Patient >18 years old, male or female, weighting more than 40 kg and with a 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)
· Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault
formula)
· Albuminaemia =1 x LLN
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· Proteinuria < 30 mg/dL on dipstick; in case of proteinuria = 30 mg/dL, 24-hour proteinuria = 1.5 g/24 h
8. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative
pregnancy test), who agrees to 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. Acceptable forms of contraception include:
o A documented placement of an intrauterine device (IUD) or intrauterine system (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)
o Documented tubal ligation (female sterilization). In addition, a barrier method used with spermicidal foam/gel/film/cream/suppository) should also be used
o Double barrier method with
spermicidal foam/gel/film/cream/suppository
o Any other contraceptive method with a documented failure rate of <1% per year
o 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:
o Condom;
o 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:
o Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository;
o 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);
o Your female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable
progesterone or subdermal implants and

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

Study & Design

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