A Prospective Study of Cabazitaxel in Patients With Non Seminomatous Germ-cell Tumors

Study Overview
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Brief Summary
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Cabazitaxel is a new generation taxane with a high capacity for blood-brain barrier crossing and limited peripheral neuro-toxicity, two major potential advantages in patients with advanced NSGCTs. Cabazitaxel has a broader in vitro spectrum of activity than docetaxel. Taxanes have demonstrated activity in pre-treated GCTs and are now part of standard treatment, but cabazitaxel has not yet been tested in patients with NSGCT.

Official Title
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A Prospective Phase II Trial of Cabazitaxel in Male Patients With Chemotherapy Pre-treated Metastatic Nonseminomatous Germ-cell Tumors

Conditions
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Non-seminomatous Germ-cell Tumors

Intervention / Treatment
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* Drug: Cabazitaxel


Participation Criteria
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Eligibility Criteria
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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 : Hemoglobin >/= 10.0 g/dL Absolute neutrophil count >/= 1.5 x 10 ^ 9/L, Platelet count >/= 100 x 10 ^ 9/L, Adequate organ function Serum 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 AST/SGOT and ALT/SGPT </= 1.5 x ULN Bilirubin </= 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 Exclusion Criteria: Patients receiving anti cancer therapy 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 Patients who have had a major surgery within 4 last weeks prior enrolment Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of congestive heart failure (NYHA III or IV) or myocardial infarction within last 6 months is also not allowed

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel<br> | Drug: Cabazitaxel<br>* On Day 1 of each cycle, patients will receive cabazitaxel at a dose of 25 mg/m², administered by IV route in 1 hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Favorable response | To evaluate the favorable response rate of cabazitaxel treatment in patients with highly-pretreated nonseminomatous germ-cell tumors (NSGCT) | Assessed every 6 weeks from start of treatment up to 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate on brain metastases | MRI of the brain every 6 weeks only in case of brain metastases detected at baseline and for all patients at the end of the study. Evaluation will be made using RECIST V1.1 | Assessed every 6 weeks after treatment start up to 72 months | 
| Progression free survival |  | Assessed every 6 weeks from treatment start to progression up to 72 months | 
| Overall survival |  | Assessed every 3 weeks after treatment start up to 72 months |