A Study to Evaluate the Effects of Combining Cabazitaxel With Cisplatin Given Every 3 Weeks in Patients With Advanced Solid Cancer

Study Overview
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Brief Summary
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This study is designed as a phase 1, multicenter, open-label, single arm, dose-escalation, study of Cabazitaxel in combination with cisplatin, to determine safety, pharmacokinetics (PK), and efficacy in solid tumors (parts 1 and 2) and single sequence, two-treatment, crossover studies to determine the effect of strong CYP3A4 inhibition and induction on the PK of Cabazitaxel in patients with solid tumors (part 3 and part 4, respectively). There are 4 parts to the study: Part 1: Determine the Dose Limiting Toxicities (DLT)'s and Maximum Tolerated Dose (MTD) based on safety. Part 2: Determine the anti-tumor activity of the combination regimen at the Maximum Tolerated Dose (MTD) in an extended cohort of patients. Part 3: Determine the effect of a strong CYP3A4 inhibitor (ketoconazole) on the pharmacokinetic (PK) of Cabazitaxel. Part 4: Determine the effect of a strong CYP3A4 inducer (rifampin) on the pharmacokinetic (PK) of Cabazitaxel.

Detailed Description
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The total duration on the study per subject will be about 26 weeks broken down as follows: A maximum of 21-day screening phase, 21-days (+/- 2 weeks) study treatment cycles, 30-day follow-up visit after the last dose of study medication. Cut-off date for parts 1, 2, 3 and 4: when the last patient has completed 6 cycles (parts 1 and 2) or 2 cycles (parts 3 and 4) of treatment or discontinued study treatment (for disease progression, unacceptable toxicity, withdrawal of consent, or investigator's decision to withdraw), whichever comes first, in the corresponding part. Patients still receiving treatment at the cut-off date may continue to receive treatment beyond the cut-off date at investigator's discretion if benefiting.

Official Title
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A Dose-Escalation Study Of The Safety, Tolerability, And Pharmacokinetics Of Cabazitaxel In Combination With Cisplatin Administered Every 3 Weeks In Subjects With Advanced Solid Malignancies

Conditions
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Solid Cancer

Intervention / Treatment
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* Drug: cabazitaxel (XRP6258)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: confirmed metastatic or unremovable advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist, but for which cisplatin based therapy is appropriate signed informed consent Exclusion criteria limited physical functioning (as evaluated by the Eastern Cooperative Oncology Group (ECOG) scale) inability to follow study requirements and schedule treatment of cancer within 3 weeks of study, concurrent treatment in another clinical trial or with any other cancer therapy serious medical illness at same time of study and/or significantly abnormal lab reports lack of pregnancy contraception (women of childbearing potential), pregnancy, or breast feeding. Women of childbearing potential not protected by highly effective contraceptive method of birth control OTHER than hormonal contraception (Part 4 only). prior significant hearing or kidney problems continued toxic effects of prior chemotherapy cancers that cannot be physically measured (Part 2 only) The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>5, 15, 20 or 25 mg/m2 one injection of cabazitaxel on day 1 of each cycle (3 weeks) | Drug: cabazitaxel (XRP6258)<br>* administered by IV infusion in addition to cisplatin treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT)'s of the combination of cabazitaxel and cisplatin (part 1) |  | first cycle (i.e.3 weeks) | 
| Objective response ratio (Complete response (CR) and partial response (PR)) (part 2) |  | up to 6 cycles, ie 18 weeks | 
| Pharmacokinetics (PK) of cabazitaxel (part 3 and 4) |  | up to 6 cycles, ie 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP) (part 1 and 2) |  | up to 6 cycles, ie 18 weeks | 
| Duration of response (DR) (Part 1 and 2) |  | up to 6 cycles, ie 18 weeks | 
| Cabazitaxel pharmacokinetic (part 1 and 2) |  | up to 6 cycles, ie 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, XRP6258, cisplatin, Antineoplastic Combined Chemotherapy Protocols