Solid Cancer
Conditions
Keywords
Phase 1, XRP6258, cisplatin, Antineoplastic Combined Chemotherapy Protocols
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.
Interventions
* administered by IV infusion * in addition to cisplatin treatment
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed