A comparison study to look at the safety and effectiveness of a new drug (masitinib) for treating a prostrate cancer which can spread and which is not easily to be removed against a currently used treatment (docetaxel & prednisone).

• Register: EUCTR
• Last refreshed on: 27 July 2020
• Main ID: EUCTR2013-000809-23-GB
• Date of registration: 18/08/2014
• Prospective Registration: No
• Primary sponsor: AB Science
• Public title: A comparison study to look at the safety and effectiveness of a new drug (masitinib) for treating a prostrate cancer which can spread and which is not easily to be removed against a currently used treatment (docetaxel & prednisone).
• Scientific title: A prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel groups, phase 3 study to compare the efficacy and safety of masitinib in combination with docetaxel to placebo in combination with docetaxel in first line metastatic Castrate Resistant Prostate Cancer (mCRPC). - Phase 3 Masitinib/Placebo + Docetaxel in Metastatic Prostate Cancer V1
• Date of first enrolment: 07/08/2014
• Target sample size: 580
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000809-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Canada, China, Czech Republic, Greece, Hong Kong, Hungary, India, Italy, Korea, Democratic People's Republic of, Malaysia, Mexico, Morocco, Peru, Philippines, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Project Manager
• Affiliation: AB Science

• Name: Project Manager
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient aged = 18 years old, with histologically or cytologically confirmed metastatic Castrate Resistant Prostate Cancer (medical or surgical castration: androgens deprivation by GnHR agonist or antagonist or patient with surgical castration; hormonal castration confirmed biologically (testosterone < 0.5ng/ml) with one of the following criteria:
- Pre-treated with abiraterone with progressed disease documented, OR
- with indication for initiating docetaxel administration (e.g., widespread visceral disease or rapidly progressive disease).
- *If surgical castration is done than there will be no requirement to perform testosterone test.
2. Patient with evidence of progressive metastatic disease. Disease progression at trial enrolment is based on progression in at least one variable described in Table 4
3. Patient with ECOG = 1
4. Patient with adequate organ function:
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Haemoglobin = 10 g/dL
- Platelets (PTL) = 75 x 109/L
- AST and ALT = 3x ULN ((=5 x ULN in case of liver metastases)
- Gamma GT =2.5 x ULN (=5 x ULN in case of liver metastases)
- Bilirubin = 1.5x ULN (= 3 x ULN in case of liver metastasis)
- Normal creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
- Albuminaemia > 1 x LLN
- Proteinuria < 30 mg/dL (1+) on the dipstick; in case of proteinuria = 1+ on the dipstick, 24 hours proteinuria must be = 1.5g/24h
5. Patient with life expectancy > 6 months
6. Patient with BMI > 18 kg/m2 and weight > 40 kg
7. Contraception
? Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake or who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake.
? Highly effective methods of contraception include:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomized male (azoospermia assessed medically)
- Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
? Acceptable methods of contraception include:
- Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
- Male or female condom with or without spermicide
- Cap, diaphragm, or sponge with spermicide
8. Patient able and willing to comply with study procedures as per protocol
9. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent.
10. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of
Exclusion criteria:
1. Patient who has been previously treated with chemotherapy.
2. Patient with bone marrow irradiation > 40% within 12 months before baseline
3. Patient treated for a cancer other than prostate cancer within 3 years before enrolment, with the exception of basal cell carcinoma (and pTa or pT1)
4. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
- Patient with recent cardiac history (within 6 months) of:
o Acute coronary syndrome
o Acute heart failure (class III or IV of the NYHA classification)
o 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 (atrioventricular block 2 and 3, sino-atrial block)
- Syncope without known aetiology within 3 months
- Uncontrolled severe hypertension, according to the judgement of the investigator, or symptomatic hypertension
6. 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
7. Patient under treatment with any anti-tumour therapy (any radiotherapy, chemotherapy, biologic or anti-androgen therapy except GnRH/LHRH analogs)

WASH OUT
• Known hypersensitivity to masitinib or to any of the excipients
• Patients with any investigational agent within 4 weeks prior to baseline
• Patients with an active infection requiring antibiotics within 14 days prior to baseline
• Four weeks prior to baseline for anti-androgens (example. bicalutamide) and 5-alpha reductase inhibitors


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Castrate Resistant Prostate Cancer (mCRPC)
MedDRA version: 21.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Mastinib mesylate
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mastinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 119.3-238.5
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Progression Free Survival (PFS)

Main Objective: The objective is to demonstrate efficacy and evaluate safety of masitinib in combination with docetaxel and prednisone to placebo in combination with docetaxel and prednisone in first line metastatic Castrate Resistant Prostate Cancer (mCRPC).

The primary endpoint is Progression Free Survival (PFS)

Secondary Objective: The objective is to compare the efficacy (overall survival), the safety and the quality of life of masitinib at 6mg/Kg/day in combination with standard docetaxel to matching placebo in combination with standard therapy docetaxel in first line metastatic Castrate Resistant Prostate Cancer (mCRPC).

Timepoint(s) of evaluation of this end point: Every 12 weeks.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 12 weeks.

Secondary end point(s): - Key Secondary endpoint - overall Survival (OS)
- PFS rate at 6,9,12 months based on Kaplan-Meier estimate of PFS distribution
- OS rate at 12,15,18 months based on Kaplan-Meier estimate of OS distribution
- Time To Progression (TTP)
- TTP rate every 12 weeks
- Best response rate, Objective Response rate: Complete Response (CR) or Partial Response (PR) and disease control rate (CR+ PR+ SD) every 12 weeks
- Decline of PSA level = 30% from baseline at 12 weeks or later
- Quality of life assessment every 6 weeks Quality of Life according to the EORTC QLQ-C30 questionnaire
- Present Pain Intensity score based on the McGill-Melzack Pain Questionnaire (MPQ)
- Analgesic intake
- ECOG Performance Status
- Pain improvement (VAS)
- Pharmacogenomic assessment: Relationship between genomic data and overall survival.
- Safety profile using the NCI CTCAE v4.03 classification

Secondary ID(s)

116620

2013-000809-23-ES

AB12003

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 21/07/2014
Contact: