Safety and Pharmacokinetic Study of Cabazitaxel in Patients With Advanced Solid Tumors and Liver Impairment

NCT ID: NCT01140607

Last Updated: 2015-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-07-31

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.

Conditions

Neoplasm Malignant

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: normal hepatic function: cabazitaxel

cabazitaxel 25mg/m^2

IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Group Type: EXPERIMENTAL

Cabazitaxel (XRP6258)

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Cohort 2: mild hepatic impairment : cabazitaxel

cabazitaxel 20mg/m^2

IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Group Type: EXPERIMENTAL

Cabazitaxel (XRP6258)

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Cohort 3: moderate hepatic impairment: cabazitaxel

cabazitaxel 10mg/m^2

IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Group Type: EXPERIMENTAL

Cabazitaxel (XRP6258)

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Cohort 4: severe hepatic impairment: cabazitaxel

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).

Group Type: EXPERIMENTAL

Cabazitaxel (XRP6258)

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Cohort 5: normal hepatic function: cabazitaxel and midazolam

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)

Group Type: EXPERIMENTAL

Cabazitaxel (XRP6258)

Intervention Type: DRUG

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Interventions

Cabazitaxel (XRP6258)

Pharmaceutical form:solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840014

La Jolla, California, United States

Investigational Site Number 840013

Loma Linda, California, United States

Investigational Site Number 840020

Washington D.C., District of Columbia, United States

Investigational Site Number 840016

Jacksonville, Florida, United States

Investigational Site Number 840002

Tampa, Florida, United States

Investigational Site Number 840017

Decatur, Illinois, United States

Investigational Site Number 840003

Metairie, Louisiana, United States

Investigational Site Number 840019

Baltimore, Maryland, United States

Investigational Site Number 840012

Boston, Massachusetts, United States

Investigational Site Number 840001

St Louis, Missouri, United States

Investigational Site Number 840021

Canton, Ohio, United States

Investigational Site Number 840007

Cincinnati, Ohio, United States

Investigational Site Number 840010

Bethlehem, Pennsylvania, United States

Investigational Site Number 840006

San Antonio, Texas, United States

Countries

United States

Other Identifiers

U1111-1116-5845

Identifier Type: OTHER

Identifier Source: secondary_id

POP6792

Identifier Type: -

Identifier Source: org_study_id