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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 76
- Locations
- 7
- Primary Endpoint
- Objective response ratio (Complete response (CR) and partial response (PR)) (part 2)
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1
- 5, 15, 20 or 25 mg/m2
- one injection of cabazitaxel on day 1 of each cycle (3 weeks)
Intervention: cabazitaxel (XRP6258) (Drug)
Outcomes
Primary Outcomes
Objective response ratio (Complete response (CR) and partial response (PR)) (part 2)
Time Frame: up to 6 cycles, ie 18 weeks
Pharmacokinetics (PK) of cabazitaxel (part 3 and 4)
Time Frame: up to 6 cycles, ie 18 weeks
Dose Limiting Toxicities (DLT)'s of the combination of cabazitaxel and cisplatin (part 1)
Time Frame: first cycle (i.e.3 weeks)
Secondary Outcomes
- Duration of response (DR) (Part 1 and 2)(up to 6 cycles, ie 18 weeks)
- Time to progression (TTP) (part 1 and 2)(up to 6 cycles, ie 18 weeks)
- Cabazitaxel pharmacokinetic (part 1 and 2)(up to 6 cycles, ie 18 weeks)