E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castrate Resistant Prostate Cancer (mCRPC) |
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E.1.1.1 | Medical condition in easily understood language |
Modification of some prostate cells that turn into cancer cells and have spread to other organs and cannot be easily removed.
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
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). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
During this study, an ancillary pharmacogenomic study will be performed in order to confirm or define predictive criteria of overall survival from genomic data. An ancillary study aimed at finding potential DNA mutations, amplification and/or deletion that might explain short or long term survival, side effects and treatment response. Tumour biopsies of subjects willing to participate in this sub study will be collected at baseline.
In addition if a patient experiences severe neutropenia or skin toxicity a blood sample will be taken for analysis to correlate genomic data with the occurrence of these reactions. |
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E.3 | Principal 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 severe neutropenia or severe cutaneous toxicity. |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
South Africa |
Spain |
Tunisia |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Patient is treated until disease progression, limiting toxicity or consent withdrawal. Follow-up preformed until patient's death. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 30 |