Safety and Pharmacokinetic Study of Cabazitaxel in Patients With Advanced Solid Tumors and Liver Impairment
- Registration Number
- NCT01140607
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objectives:
* To determine the maximum tolerated dose (MTD) and safety of Cabazitaxel when administered to advanced solid tumor patients with varying degrees of hepatic impairment
* To determine the pharmacokinetics (PKs) of Cabazitaxel in patients with varying degrees of hepatic impairment
* To correlate PK variables with pharmacodynamic (PD) safety parameters in order to guide prescribers with regard to dosing in this patient population
* To assess the effect of cabazitaxel at recommended dose of 25mg/m\^2 on CYP3A enzyme activity using midazolam as probe in an additional cohort of cancer patients with normal hepatic function.
- Detailed Description
The study consists of:
* a screening phase (maximum length of 21-day).
* a treatment phase with 21-day study treatment cycles. Cycle lengths may be extended up to maximum of 12 additional days in case of unresolved toxicity.
Patients continue to receive treatment until they experience, unacceptable toxicities/AEs, disease progression ,withdraw their consent, or the investigator decides to discontinue the patient, or study cut-off, whichever comes first.
* a 30-day follow-up visit after the last dose of study medication.
The cut off date is when the last patient treated has completed cycle 1 and the subsequent 30 days follow-up.
Patients may continue to be treated as long as they are benefiting from study treatment and have not met study withdrawal criteria.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 3: moderate hepatic impairment: cabazitaxel Cabazitaxel (XRP6258) cabazitaxel 10mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Cohort 1: normal hepatic function: cabazitaxel Cabazitaxel (XRP6258) cabazitaxel 25mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Cohort 2: mild hepatic impairment : cabazitaxel Cabazitaxel (XRP6258) cabazitaxel 20mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Cohort 4: severe hepatic impairment: cabazitaxel Cabazitaxel (XRP6258) cabazitaxel 5 mg/m\^2 or 10mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Cohort 5: normal hepatic function: cabazitaxel and midazolam Cabazitaxel (XRP6258) cabazitaxel 25mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks). Midazolam is given orally in single dosing on day -1 and day 1 (crossover)
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLT) cycle 1 (3 weeks) A clinical adverse event or a laboratory abnormality is defined as DLT when it is drug-related as assessed by the investigator and agreed upon by the study committee.
- Secondary Outcome Measures
Name Time Method Safety investigations (physical examination, vital signs and laboratory tests) up to 30 days after the last dosing Physical examination includes Eastern Cooperative Oncology Group (ECOG) performance status and signs and symptoms.
Vital signs includes weight, temperature, blood pressure and heart rate.
Laboratory tests includes hematology, coagulation, biochemistry and urinalysis. Laboratory abnormalities are graded according to the NCI CTCAE v.4.0Cabazitaxel effect on CYP3A enzyme activity single dosing on day -1 and day 1 Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration cycle 1 (3 weeks)
Trial Locations
- Locations (14)
Investigational Site Number 840003
🇺🇸Metairie, Louisiana, United States
Investigational Site Number 840001
🇺🇸St Louis, Missouri, United States
Investigational Site Number 840020
🇺🇸Washington, District of Columbia, United States
Investigational Site Number 840010
🇺🇸Bethlehem, Pennsylvania, United States
Investigational Site Number 840013
🇺🇸Loma Linda, California, United States
Investigational Site Number 840019
🇺🇸Baltimore, Maryland, United States
Investigational Site Number 840021
🇺🇸Canton, Ohio, United States
Investigational Site Number 840017
🇺🇸Decatur, Illinois, United States
Investigational Site Number 840007
🇺🇸Cincinnati, Ohio, United States
Investigational Site Number 840006
🇺🇸San Antonio, Texas, United States
Investigational Site Number 840012
🇺🇸Boston, Massachusetts, United States
Investigational Site Number 840014
🇺🇸La Jolla, California, United States
Investigational Site Number 840002
🇺🇸Tampa, Florida, United States
Investigational Site Number 840016
🇺🇸Jacksonville, Florida, United States