Study to evaluate 2 types of treatment as first line treatment (masitinib + docetaxel or placebo + docetaxel ) in the treatment of patients with metastatic Castrate Resistant Prostate Cancer (mCRPC)

• Register: EUCTR
• Last refreshed on: 10 October 2016
• Main ID: EUCTR2013-000809-23-CZ
• Date of registration: 26/05/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Study to evaluate 2 types of treatment as first line treatment (masitinib + docetaxel or placebo + docetaxel ) in the treatment of patients with metastatic Castrate Resistant Prostate Cancer (mCRPC)
• 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)
• Date of first enrolment: 22/09/2014
• Target sample size: 580
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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, Republic of, Malaysia, Mexico, Morocco, Peru, Philippines, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Tunisia, Ukraine, United Kingdom, United States

Contacts

• Name: Alain Moussy
• Affiliation: AB Science

• Name: Alain Moussy
• 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).
2. Patient with evidence of progressive metastatic disease. Disease progression at trial enrolment is based on progression in at least one variable as described in Table 4. Error! Reference source not found..
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; if proteinuria = 1+ on the dipstick, 24 hours proteinuria must be = 1.5g/24h
5. Patient with life expectancy > 3 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 severe neutropenia or severe cutaneous toxicity

Are the trial subj
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:
• 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 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 (ex. 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]

metastatic Castrate Resistant Prostate Cancer (mCRPC).

Intervention(s)

Product Name: masitinib 100mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MASITINIB MESYLATE
CAS Number: 1048007-93-7
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: masitinib 200mg
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: MASITINIB MESYLATE
CAS Number: 1048007-93-7
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Key Secondary endpoint
• Overall Survival (OS)
Secondary endpoint
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

Timepoint(s) of evaluation of this end point: Date of documented death

Main Objective: Progression Free Survival (PFS)

Primary end point(s): The primary objective of the study is to determine whether masitinib daily plus docetaxel and prednisone according to usual practice prolongs progression-free survival (PFS) as compared to placebo plus docetaxel and prednisone according to usual practice in
i. all patients (overall population) or
ii. the targeted sub-population (patients with Alkaline phosphatase levels =250 ng/ml)

Secondary Outcome(s)

Secondary end point(s): Key-Secondary endpoint
The key-secondary objective of the study is to determine whether masitinib daily plus docetaxel and prednisone according to usual practice prolongs Overall survival (OS) as compared to placebo plus docetaxel and prednisone according to usual practice in
i. all patients (overall population) or
ii. the targeted sub-population (patients with Alkaline phosphatase levels =250 ng/ml)

OS is defined as the time from date of randomization to date of death due to any cause. If a patient is not known to have died, then OS will be censored at the date of last known date patient alive.

Other Secondary endpoints:
- 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
Overall Time To Progression (TTP) is defined as the time from the date of randomization to the date of documented progression defined according to Table 4 during the study.
- TTP rate every 12 weeks
TTP rate is defined as the number of patients without documented progression during the study divided by the number of patients in the population of analysis, estimated with Kaplan-Meier.
Best Response is defined as the best response (CR or PR or SD or PD) defined according to Table 4 recorded from the start of the treatment until end of study.
Objective Response is defined as a documented partial response (PR) or complete response (CR) defined according to Table 4.
Disease control rate (CR + PR + SD) is defined as the number of patients with documented partial response or complete response defined according to
Objective Response rate is defined as the number of patients with Objective Response divided by the total number of patients in the population of analysis.
- Decline of PSA level = 30% from baseline at 12 weeks or later

Quality of life variables
- Quality of Life is assessed as a change in absolute value and/or percentage between baseline and each time point for the following variables:
- Quality of Life according to the EORTC QLQ-C30 questionnaire
- Present Pain Intensity score based on the McGill- Melzack Pain Questionnaire (MPQ) and VAS
- Analgesic consumption score
- ECOG Performance Status
- Pain improvement (VAS)
- Pharmacogenomic assessment
- Relationship between genomic data and overall survival
Safety Variables
Safety of the study treatment will be assessed on occurrence, type, frequency and severity of adverse events (AEs) and laboratory toxicities, intake of concomitant treatments, per-treatment arising changes in physical examination, vital signs (blood pressure, pulse rate and body temperature), ECG, clinical laboratory tests (biochemistry, haematology) and urinary analysis. Safety parameters will be graded based on NCI CTCAE v4.02 classification.

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

Secondary ID(s)

AB12003

2013-000809-23-ES

Source(s) of Monetary Support

AB Science