A Study to Evaluate the Effects of Combining Cabazitaxel With Cisplatin Given Every 3 Weeks in Patients With Advanced Solid Cancer

Condition(s) targeted: Solid Cancer

Intervention: cabazitaxel (XRP6258) (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Sanofi

Official(s) and/or principal investigator(s):
Clinical Sciences & Operations, Study Director, Affiliation: Sanofi

Overall contact:
For site information, send an email with site number to, Email: Contact-Us@sanofi-aventis.com

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.

Official title: A Dose-Escalation Study Of The Safety, Tolerability, And Pharmacokinetics Of Cabazitaxel In Combination With Cisplatin Administered Every 3 Weeks In Subjects With Advanced Solid Malignancies

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Dose Limiting Toxicities (DLT)'s of the combination of cabazitaxel and cisplatin (part 1)

Objective response ratio (Complete response (CR) and partial response (PR)) (part 2)

Pharmacokinetics (PK) of cabazitaxel (part 3 and 4)

Secondary outcome:

Time to progression (TTP) (part 1 and 2)

Duration of response (DR) (Part 1 and 2)

Cabazitaxel pharmacokinetic (part 1 and 2)

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

For site information, send an email with site number to, Email: Contact-Us@sanofi-aventis.com

Investigational Site Number 840008, Los Angeles, California 90048, United States; Active, not recruiting

Investigational Site Number 840003, San Diego, California 92123, United States; Completed

Investigational Site Number 840010, Decatur, Illinois 62526, United States; Recruiting

Investigational Site Number 840002, Baltimore, Maryland 21201, United States; Completed

Investigational Site Number 840009, Detroit, Michigan 48201, United States; Recruiting

Investigational Site Number 840006, St Louis, Missouri 63110, United States; Completed

Investigational Site Number 840007, Cincinnati, Ohio 45267-0542, United States; Recruiting

Investigational Site Number 840005, San Antonio, Texas 78229, United States; Recruiting

Starting date: June 2009
Last updated: August 22, 2012