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

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2009-017918-69-SK
• Date of registration: 04/08/2010
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: 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
• Scientific title: 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
• Date of first enrolment: 10/09/2010
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017918-69
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Dacarbazine
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Czech Republic, Germany, Greece, Hungary, Italy, Slovakia, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1.Patient = 18 years old, male or female, weighting more than 40 kg
2.Patient with histologically or cytologically confirmed non-resectable or metastatic stage III (non-resectable IIIB or IIIC, AJCC TNM staging system 7th edition) or stage IV melanoma
3.Patient with detectable c-kit JM mutation 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 = 12 weeks
7.Patient with adequate organ function
• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Haemoglobin = 10 g/dL
• Platelets (PLT) = 100 x 109/L
• AST/ALT = 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)
• Creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
• Albuminaemia = 0.75 x LLN
• Urea = 2 x ULN
• Proteinuria < 30 mg/dL on dipstick; in case of proteinuria = 30 mg/dL, 24-hour proteinuria = 1.5 g/24 h
8.Man or woman of child bearing potential, (entering the study after a menstrual period and who have a negative pregnancy test) 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 three months after the last treatment intake
9.Patient able and willing to comply with study procedures as per protocol
10.Patient able to understand, and willing to sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures


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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 a disease progression after 3 months of dacarbazine therapy.
5.Prior treatment with a tyrosine kinase c-kit inhibitor
6.Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria (i.e., congestive heart failure, myocardial infarction within six months before baseline)
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
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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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: 13.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 13.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 119-
INN or Proposed INN: Masitinib mésylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 238-

Primary Outcome(s)

Primary end point(s): Primary endpoint:
Progression Free Survival (PFS) defined as the delay between the date of randomization to the date of documented progression (according to m-RECIST) or any cause of death during the study

Main Objective: The primary objective is to compare the efficacy 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 (c-kit JM).
The primary endpoint is Progression Free Survival (PFS).

Secondary Objective: Secondary objectives are to compare the efficacy and safety of masitinib at 7.5 mg/kg/day to dacarbazine
The secondary endpoints are:
Efficacy:
• Overall Survival (OS)
• Survival rate at week 6, 12, 18, 24 and every 12 weeks
• PFS rate at week 6, 12, 18, 24 and every 12 weeks
• Time To Progression (TTP) and TTP rate at week 6, 12, 18, 24 and every 12 weeks
• Best response rate, Objective response rate (CR + PR) and Disease control rate (CR + PR + SD)
Quality of life : assessment at week 6, 12, 18 and 24 and every 12 weeks
• ECOG performance status
• EORTC QLQ-C30
Safety profile using the NCI CTCAE v4.0 classification

Secondary ID(s)

AB08026