| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic castrate-resistant prostate cancer requiring initiation of chemotherapy |
| Cancer de la prostate métastatique résistant à la castration nécessitant l'initiation de la chimiothérapie |
|
| E.1.1.1 | Medical condition in easily understood language |
| Not Applicable |
| Non applicable |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| 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 primary objective of this study is to compare the biological activity of cabazitaxel (6 cycles) to that of docetaxel (6 cycles) in metastatic castrate-resistant prostate cancer (mCRPC) patients with docetaxel resistant mCPRC defined as ≥ 5CTCs/7.5ml after 2 cycles of docetaxel. |
| L’objectif principal de l’étude est de comparer l’activité biologique du cabazitaxel (6 cycles de traitement) à celle du docétaxel (6 cycles de traitement) chez des patients atteints d’un cancer métastatique de la prostate résistant à la castration (CPRCm) et au docétaxel défini par un nombre de CTC ≥ 5 /7,5 ml après 2 cycles de traitement par docétaxel (Groupe II) |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are the following:
1. In patients with docetaxel resistant mCRPC (≥5CTCs/7.5ml after 2 cycles of docetaxel), comparison of cabazitaxel (6 cycles) to docetaxel (6 cycles) in terms of:
- Prostate Specific Antigen PSA progression-free-survival (PSA-PFS)
- Radiographic progression-free-survival (PFS, as per RECIST v1.1)
- Time to pain progression
- Safety profile of each treatment graded according to the NCI CTCAE version 4.0 scale (Appendix 2)
- Disease specific survival (DSS)
- Overall survival (OS)
2. In patients with docetaxel sensitive mCRPC (< 5 CTCs/7.5 ml after 2 cycles of docetaxel):
- CTC assessment at the end of 6 additional cycles of docetaxel
- PSA progression-free-survival (PSA-PFS)
- Radiographic progression-free-survival (PFS, as per RECIST v1.1)
- Time to pain progression
- Safety profile of each treatment graded according to the NCI CTCAE version 4.0 scale (Appendix 2)
- Disease specific survival (DSS)
- Overall survival (OS) |
1.Patients atteints d’un CPRCm et résistant au docétaxel (nombre de CTC ≥ 5/7,5 ml après 2cycles de traitement par docétaxel) (Groupe II):Comparaison des effets d’un traitement par cabazitaxel (6 cycles) par rapport à traitement par docétaxel (6 cycles)Survie sans progression du taux de PSA,Survie sans progression radiologique selon critères RECIST v1.1,Délai d’apparition de la douleur, Profil de tolérance de chaque traitement évalué selon NCI-CTCAE v4.0, Survie spécifique à la maladie (DSS), Survie globale (SG)
2.Patients atteints d’un CPRCm et sensible au docétaxel (nombre de CTC < 5 /7,5 ml après 2 cycles de traitement par docétaxel) (Groupe I):Énumération CTC à la fin des 6 cycles de traitement par docétaxel,Survie sans progression du taux de PSA (SSP - PSA),Survie sans progression radiographique (SSPr) selon les critères RECIST v 1.1,Délai d’apparition de la douleur,Profil de tolérance de traitement évalué selon NCI CTCAE v4.0,Survie spécifique à la maladie (DSS) ,globale (SG) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
To be eligible, the patients must fulfill the following inclusion criteria:
1. Written informed consent signed prior any study-related procedures
2. Male ≥ 18 years
3. Histologically confirmed diagnosis of prostate adenocarcinoma
4. Metastatic disease as evidenced by medical imaging techniques (bone scan, CT scan, MRI and/or PET) according to the RECIST 1.1.
5. Castrate resistant disease defined by testosterone levels ≤ 50 ng/dl under continuous hormonal treatment with LH-RH agonist/antagonist or after surgical castration
6. Progressive (biological and/or radiological) disease requiring chemotherapy subsequent to any type of hormonal therapy
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix 1)
8. Patient with screening CTC count ≥ 5/7.5 ml
9. Patient must agree to use effective contraception during the trial and for a period of at least 6 months following the last administration of treatment
10. Patient must be affiliated to the Social Security System |
Pour être éligible à cette étude, les patients doivent répondre aux critères d’inclusion suivants :
1. Le formulaire de consentement éclairé doit être signé avant la réalisation de toute procédure associée à l’étude
2. Homme âgé de 18 ans ou plus
3. Diagnostic d’un adénocarcinome de la prostate confirmé par des analyses histologiques
4. Maladie métastatique mise en évidence par des techniques d’imagerie médicale (scintigraphie osseuse, TDM, IRM et/ou TEP) selon les critères RECIST v. 1.1.
5. Maladie résistante à la castration définie par des taux de testostérone ≤ 50 ng/dl sous un traitement hormonal continu par agonistes/antagonistes de la LH-RH ou après castration chirurgicale
6. Progression de la maladie (biologique et/ou radiologique) nécessitant une chimiothérapie due à la prise de tout type d’hormonothérapie
7. Indice de performance Eastern Cooperative Oncology Group (ECOG) ≤ 2 (annexe 1)
8. Patient dont le nombre de CTC ≥ 5 / 7,5 ml à la période de sélection
9. Le patient doit accepter d’utiliser une méthode de contraception efficace pendant toute la durée de l’essai et ce pendant une période d’au moins 6 mois suivant l’administration de la dernière dose de traitement
10. Le patient doit être affilié au système de sécurité sociale |
|
| E.4 | Principal exclusion criteria |
Patient must not be enrolled if he meets any of the following non-inclusion criteria:
1. Prior chemotherapy for metastatic prostate cancer with the exception of estramustine:
• < 1 year from the end of adjuvant and/or neoadjuvant chemotherapy for localized disease
• < 1 year from the end of chemotherapy for de novo metastatic prostate cancer
2. Prior isotope therapy, radiotherapy to the whole pelvic area or radiotherapy to > 30% of bone marrow
3. Less than 1 month elapsed from the end of a prior treatment with radiotherapy, surgery and less than 2 weeks from any previous hormonal treatment except for LH-RH agonists/antagonists (which are to be continued). Prior to study entry, patients may be treated with bisphosphonates which should be pursued.
4. History of brain metastases, uncontrolled spinal cord compression, carcinomatous meningitis or new evidence of brain or leptomeningeal disease
5. Patient with any of the following abnormal laboratory tests:
• Bone marrow function: hemoglobin < 10 g/dl, absolute neutrophil count < 1.5 x 109/L, platelets < 100 x 109/L,
• Hepatic function: AST/SGOT and/or ALT/SGPT > 1.5 x upper limit of normal (ULN), total bilirubin > 1.0 ULN (except patients with liver metastases),
• Renal function: creatinine clearance < 40 ml/min (MDRD)
6. History of hypersensitivity to cabazitaxel, to other taxanes or polysorbate 80 or any of its excipients
7. History of hypersensitivity todocetaxel or polysorbate 80 or any of its excipients
8. Contraindication to corticosteroids
9. Peripheral neuropathy grade ≥ 2 according to NCI CTCAE v. 4.0
10. Ventricular ejection fraction < 50% (echography or scintigraphy)
11. Any of the following within 6 months prior to study entry: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack
12. Any of the following within 3 months prior to study entry: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, inflammatory bowel disease, pulmonary embolism or other uncontrolled thromboembolic event
13. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormally that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
14. Planned vaccination with a live or live-attenuated vaccines
15. Participation in another clinical trial and any treatment with any investigational drug within 30 days prior to randomization
16. Any illness or problem including geographic, psychiatric or psychological which is incompatible with being monitored during the trial
17. Person deprived of their liberty or under protective custody or guardianship |
Le patient ne doit pas être inclus dans l’essai s’il répond à l’un des critères de non-inclusion suivants :
1. Chimiothérapie antérieure pour le traitement d’un cancer métastatique de la prostate, à l’exception de l’estramustine :
• < 1 an à compter de la fin de la chimiothérapie adjuvante et/ou néoadjuvante pour traiter une maladie localisée
• < 1 an à compter de la fin de la chimiothérapie pour traiter un cancer métastatique de la prostate de novo
2. Traitement antérieur par isotopes, radiothérapie de toute la zone pelvienne ou radiothérapie sur > 30 % de la moelle osseuse
3. Moins d’1 mois depuis la fin d’un traitement antérieur par radiothérapie ou chirurgie et moins de 2 semaines depuis la fin de tout traitement hormonal antérieur, sauf pour les agonistes/antagonistes de la LH-RH (qui doivent être poursuivis). Avant de participer à l’étude, les patients traités par bisphosphonates peuvent continuer le traitement.
4. Antécédents de métastases cérébrales, compression médullaire non contrôlée, méningite carcinomateuse ou nouveau signe d’une maladie cérébrale ou leptoméningée
5. Patient présentant tout résultat anormal aux analyses biologiques suivantes :
• Fonction médullaire : taux d’hémoglobine < 10 g/dl, neutrophiles < 1,5 x 109/l, plaquettes < 100 x 109/l,
• Fonction hépatique : ASAT/SGOT et/ou ALT/SGPT > 1,5 x Limite Supérieure de la Normale (LSN), taux de bilirubine totale > 1,0 x LSN (sauf pour les patients présentant des métastases hépatiques),
• Fonction rénale : clairance de la créatinine < 40 ml/min. (formule MDRD) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Biological activity of chemotherapy as defined as < 5 CTCs per 7.5 ml at the end of 6 cycles of chemotherapy with docetaxel or cabazitaxel. The CellSearch® CTC Test (Janssen) will be used to assess CTCs (Appendix 5). Patients who could not receive the 6 cycles of treatment or the absence of biological activity will be claimed (even in the presence of CTC count). |
| Activité biologique de la chimiothérapie définie comme <5 CTC par 7,5 ml à la fin de 6 cycles de chimiothérapie avec docetaxel ou cabazitaxel. Le test CTC CellSearch® (Janssen) sera utilisé pour évaluer les CTC (annexe 5). Les patients qui n'ont pas pu recevoir les 6 cycles de traitement ou l'absence d'activité biologique seront réclamés (même en présence de numération CTC). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 4 weeks (with 7 days windows allowed) after the day of the last cycle of treatment. |
| 4 semaines (avec une fenêtre de tolérance de 7 jours) après le jour du dernier cycle de traitement. |
|
| E.5.2 | Secondary end point(s) |
RANDOMIZED TRIAL:
• PSA Progression Free Survival (PFS) is defined as time from randomization until first evidence of PSA progression or until death from any cause, whichever comes first.
- PSA progression is defined by the criteria of the Prostate cancer Clinical Trials Working Group [23] as an increase of 25% relative to reference PSA value and increase in the absolute value PSA level by at least 5 ng/ml and confirmed by a second value at least 4 weeks later or a ≥ 50% increase over nadir, provided that the increase is a minimum of 5 ng/ml and confirmed by a second value at least 1 week later.
- PSA values will be assessed at each cycle of chemotherapy.
• Radiological PFS is defined as time from randomization until first evidence of PSA progression or until death from any cause, whichever comes first.
- PSA progression is defined by the criteria of the Prostate cancer Clinical Trials Working Group [23] as an increase of 25% relative to reference PSA value and increase in the absolute value PSA level by at least 5 ng/ml and confirmed by a second value at least 4 weeks later or a ≥ 50% increase over nadir, provided that the increase is a minimum of 5 ng/ml and confirmed by a second value at least 1 week later.
- PSA values will be assessed at each cycle of chemotherapy.
• Time to pain progression is defined as time from randomization until first evidence of PSA progression or until death from any cause, whichever comes first.
- PSA progression is defined by the criteria of the Prostate cancer Clinical Trials Working Group [23] as an increase of 25% relative to reference PSA value and increase in the absolute value PSA level by at least 5 ng/ml and confirmed by a second value at least 4 weeks later or a ≥ 50% increase over nadir, provided that the increase is a minimum of 5 ng/ml and confirmed by a second value at least 1 week later.
- PSA values will be assessed at each cycle of chemotherapy.
• Time to pain progression is defined as the time from randomization to the first documentation of pain progression.
- Pain progression is defined as an increase of 1 point in the Median Personal Pain Intensity (PPI) from its nadir noted on 2 consecutive 3-week-apart visits or 25% increase in the mean analgesic score compared with the reference score (noted on 2 consecutive 3-week-apart visits or requirement for local palliative radiotherapy).
- Evaluation of the PPI & analgesic scores are based on the short-form McGill Pain Questionnaire (Appendix 6) which consists of 15 descriptors which are rated on an intensity scale as 0=none (best) 1=moderate 3=severe (worst) (TOTAL: 0=best 45=worst).
- Pain will be assessed every 2 cycles of chemotherapy.
• Disease Specific Survival (DSS) is defined as the delay between the date of randomization and the date of prostate cancer death.
• Overall Survival (OS) is defined as the delay between the date of randomization and the date of death from any cause.
PROSPECTIVE COHORT:
We will rely on the same definitions as for the randomized trial. For survival endpoints, delay will be assessed starting from the date of the CTC count following the 2 cycles of Docetaxel.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Progression or death. |
| Progression ou décès. |
|
| 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 | No |
| E.6.5 | Efficacy | No |
| 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 | No |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 20 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
Print
