Clinical trial NCT01140607: Safety and Pharmacokinetic Study of Cabazitaxel in Patients With Advanced Solid Tumors and Liver Impairment
Official title: Phase I Safety and Pharmacokinetic Study of XRP6258 (Cabazitaxel) In Advanced Solid Tumor Patients With Varying Degrees of Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Malignant
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-06-09
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

* Patients with a diagnosis of advanced, measurable or non-measurable, non-hematological cancer who have varying degrees of hepatic impairment. The cancer must be one that is either refractory to standard therapy or for which no standard therapy exists.

Exclusion criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status (PS) \>2
* Life expectancy \<3 months
* Need for a major surgical procedure or radiation therapy during the study
* Evidence of another active malignancy
* Prior chemotherapy, other investigational drug, biological therapy, targeted non-cytotoxic therapy and radiotherapy within 3 weeks prior to registration
* Patients with known history of Gilbert's syndrome
* Prior treatment with Cabazitaxel and a history of severe (Grade ≥3) hypersensitivity to taxanes, polysorbate-80, or to compounds with similar chemical structures
* Prior history of bone marrow transplant
* Any treatment known to induce CYP isoenzymes or to inhibit CYP3A4 activities within 2 weeks before or during the test period of the pharmacokinetic sampling. Moderate inhibitors within one week prior and during the pharmacokinetic sampling.
* Any contra-indications to midazolam, according to the applicable labeling.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLT)
timeFrame: cycle 1 (3 weeks)
Secondary outcomes:
measure: Safety investigations (physical examination, vital signs and laboratory tests)
timeFrame: up to 30 days after the last dosing
measure: Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration
timeFrame: cycle 1 (3 weeks)
measure: Cabazitaxel effect on CYP3A enzyme activity
timeFrame: single dosing on day -1 and day 1
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Investigational Site Number 840014
state: California
city: Loma Linda
country: United States
facility: Investigational Site Number 840013
state: California
city: Washington
country: United States
facility: Investigational Site Number 840020
state: District of Columbia
city: Jacksonville
country: United States
facility: Investigational Site Number 840016
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 840002
state: Florida
city: Decatur
country: United States
facility: Investigational Site Number 840017
state: Illinois
city: Metairie
country: United States
facility: Investigational Site Number 840003
state: Louisiana
city: Baltimore
country: United States
facility: Investigational Site Number 840019
state: Maryland
city: Boston
country: United States
facility: Investigational Site Number 840012
state: Massachusetts
city: St Louis
country: United States
facility: Investigational Site Number 840001
state: Missouri
city: Canton
country: United States
facility: Investigational Site Number 840021
state: Ohio
city: Cincinnati
country: United States
facility: Investigational Site Number 840007
state: Ohio
city: Bethlehem
country: United States
facility: Investigational Site Number 840010
state: Pennsylvania
city: San Antonio
country: United States
facility: Investigational Site Number 840006
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: