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

NCT01140607 | Completed Phase 1

• 2 other identifiers: POP6792U1111-1116-5845
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 14

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.

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicities (DLT)

  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.

  cycle 1 (3 weeks)

Secondary Outcomes (3)

• Safety investigations (physical examination, vital signs and laboratory tests)

  up to 30 days after the last dosing

• Pharmacokinetic profile of Cabazitaxel (AUC, Cmax, t1/2, CL, and Vss) from plasma concentration

  cycle 1 (3 weeks)

• Cabazitaxel effect on CYP3A enzyme activity

  single dosing on day -1 and day 1

Study Arms (5)

Cohort 1: normal hepatic function: cabazitaxel

EXPERIMENTAL

cabazitaxel 25mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)

Cohort 2: mild hepatic impairment : cabazitaxel

EXPERIMENTAL

cabazitaxel 20mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)

Cohort 3: moderate hepatic impairment: cabazitaxel

EXPERIMENTAL

cabazitaxel 10mg/m\^2 IV infusion of Cabazitaxel is given over 1 hour on Day 1 of each cycle (every 3 weeks).

Drug: Cabazitaxel (XRP6258)

Cohort 4: severe hepatic impairment: cabazitaxel

EXPERIMENTAL

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).

Drug: Cabazitaxel (XRP6258)

Cohort 5: normal hepatic function: cabazitaxel and midazolam

EXPERIMENTAL

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)

Drug: Cabazitaxel (XRP6258)

Interventions

Cabazitaxel (XRP6258) DRUG

Pharmaceutical form:solution for infusion Route of administration: intravenous

Cohort 1: normal hepatic function: cabazitaxel; Cohort 2: mild hepatic impairment : cabazitaxel; Cohort 3: moderate hepatic impairment: cabazitaxel; Cohort 4: severe hepatic impairment: cabazitaxel; Cohort 5: normal hepatic function: cabazitaxel and midazolam

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (14)

Investigational Site Number 840014

La Jolla, California, 92093, United States

Location

Investigational Site Number 840013

Loma Linda, California, 92354, United States

Location

Investigational Site Number 840020

Washington D.C., District of Columbia, 20037, United States

Location

Investigational Site Number 840016

Jacksonville, Florida, 32207, United States

Location

Investigational Site Number 840002

Tampa, Florida, 33612, United States

Location

Investigational Site Number 840017

Decatur, Illinois, 62526, United States

Location

Investigational Site Number 840003

Metairie, Louisiana, 70006, United States

Location

Investigational Site Number 840019

Baltimore, Maryland, 21201, United States

Location

Investigational Site Number 840012

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 840001

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840021

Canton, Ohio, 44718, United States

Location

Investigational Site Number 840007

Cincinnati, Ohio, 45267-0542, United States

Location

Investigational Site Number 840010

Bethlehem, Pennsylvania, 18015, United States

Location

Investigational Site Number 840006

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

cabazitaxel; XRP6258

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: June 9, 2010
• Study Start: May 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: July 21, 2015

Record last verified: 2015-07

Locations

US (14)