A Study to Evaluate the Effects of Combining Cabazitaxel With Cisplatin Given Every 3 Weeks in Patients With Advanced Solid Cancer
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Dose Limiting Toxicities (DLT)'s of the combination of cabazitaxel and cisplatin (part 1) [ Time Frame: first cycle (i.e.3 weeks) ] [ Designated as safety issue: Yes ]
- Objective response ratio (Complete response (CR) and partial response (PR)) (part 2) [ Time Frame: up to 6 cycles, ie 18 weeks ] [ Designated as safety issue: No ]
- Pharmacokinetics (PK) of cabazitaxel (part 3 and 4) [ Time Frame: up to 6 cycles, ie 18 weeks ] [ Designated as safety issue: No ]
- Time to progression (TTP) (part 1 and 2) [ Time Frame: up to 6 cycles, ie 18 weeks ] [ Designated as safety issue: No ]
- Duration of response (DR) (Part 1 and 2) [ Time Frame: up to 6 cycles, ie 18 weeks ] [ Designated as safety issue: No ]
- Cabazitaxel pharmacokinetic (part 1 and 2) [ Time Frame: up to 6 cycles, ie 18 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Drug: cabazitaxel (XRP6258)
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.
|United States, California|
|Investigational Site Number 840008|
|Los Angeles, California, United States, 90048|
|Investigational Site Number 840003|
|San Diego, California, United States, 92123|
|United States, Illinois|
|Investigational Site Number 840010|
|Decatur, Illinois, United States, 62526|
|United States, Maryland|
|Investigational Site Number 840002|
|Baltimore, Maryland, United States, 21201|
|United States, Missouri|
|Investigational Site Number 840006|
|St Louis, Missouri, United States, 63110|
|United States, Ohio|
|Investigational Site Number 840007|
|Cincinnati, Ohio, United States, 45267-0542|
|United States, Texas|
|Investigational Site Number 840005|
|San Antonio, Texas, United States, 78229|
|Study Director:||Clinical Sciences & Operations||Sanofi|