E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with pre-treated metastatic and /or primary mediastinal non-seminomatous germ-cell tumors |
patients atteints de tumeur germinale non séminomateuse (TGNS) métastatique et/ ou médiastinale primitive déjà pré traités |
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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 |
•To evaluate the favorable response rate of cabazitaxel treatment in patients with highly-pretreated non-seminomatous germ-cell tumors (NSGCT) |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the response rate on brain metastases;
•To evaluate the progression free survival
•To evaluate overall survival of patients.
•To evaluate the toxicity associated with the treatment regimen; |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male patients aged 15 years or older
•Evidence of advanced NSGCT documented either by pathology or by elevated tumor markers (AFP or hCG) and a compatible clinical presentation
•Primary site located in either the testis, the retroperitoneum or the mediastinum
•Progressive disease after at least 2 lines of chemotherapy for advanced NSGCT (ie, non stage I)
•In case of brain metastases, confirm that patients should be stable/ controlled with corticosteroid/anti seizures agents
•No other progressive carcinoma within previous the 5 years, except for basal-cell carcinoma of the skin
•Life expectancy ≥ 3 months
•Adequate hematologic function :
oHemoglobin 10.0 g/dL
oAbsolute neutrophil count 1.5 x 109/L,
oPlatelet count 100 x 109/L,
•Adequate organ function
oSerum creatinine <1.5 x ULN. If serum creatinine 1.0 - 1.5 x ULN, creatinine clearance calculated (or measured) according to CKD-EPI formula (see Appendix B) > 60 mL/min
oAST/SGOT and ALT/SGPT ≤ 1.5 x ULN
oBilirubin ≤ 1.5 x ULN
•Information delivered to patient and informed consent form signed by the patient or his legal representative
•Patient affiliated to a social security system or beneficiary of the same
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E.4 | Principal exclusion criteria |
•Patients receiving an investigational drug within 4 weeks prior to enrolment
•Previous radiotherapy within 4 weeks prior to enrolment
•Serious uncontrolled concurrent medical illness
•History of severe hypersensitivity reaction (≥grade 3) to polysorbate 80 containing drugs or to other taxanes
•Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (see Appendix A). A one week wash-out period is necessary for patients who are already on these treatments.
•Patient with reproductive potential not implementing accepted and effective method of contraception for up to 6 months after the last dose of cabazitaxel.
•Active Grade ≥3 peripheral neuropathy
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E.5 End points |
E.5.1 | Primary end point(s) |
• Favorable response:
- Complete response (CR) rate (including cCR, pCR, and sCR)
- Partial response rate with negative tumor markers (PRm-)
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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) |
•Response rate of brain metastases (RECIST V1.1)
•Progression free survival
•Overall survival
•Toxicity (NCI CTCAE v4.0), including neurotoxicity (patients being pretreated with cisplatin)
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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 | 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 | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 6 |
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 | No |
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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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 | |
E.8.9.1 | In the Member State concerned days | |