Clinical trial NCT01001221
Conditions: Neoplasms, Malignant
Sponsor: Sanofi
Start date: 2009-11-01; Completion date: 2011-10-01
Enrollment: 19 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Primary Objectives:

* Study part 1: To determine the Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicities (DLTs) of cabazitaxel administered as a 1-hour infusion in combination with gemcitabine, every 3 weeks in patients with advanced solid malignancies.
* Study part 2: To determine the antitumor activity of cabazitaxel in combination with gemcitabine, in an additional extended cohort of 15 patients with advanced solid malignancies treated with the defined MTD, as assessed by objective response rate (ORR) according to the revised guideline for Response Evaluation Criteria in Solid Tumours (RECIST 1.1 criteria).

Secondary Objectives:

* To assess the safety profile of the combination regimen of cabazitaxel with gemcitabine.
* To assess the pharmacokinetics (PK) of cabazitaxel, gemcitabine and its metabolite 2',2' difluorodeoxyuridine (dFdU) when given in combination.
* To determine Time to Progression (TTP), Objective Response Rate (ORR), and Duration of Response (DR), in the extended cohort of patients treated at the MTD in Part 2 of the study and the patients who received the MTD in Part 1 component.

For study part 1, dose levels were to be escalated according to predefined dose escalation decision rules. The Maximum Administered Dose (MAD) was reached at the dose level when at least 2 patients developed a DLT during the first 3 weeks of treatment. There was no further dose escalation when this dose was achieved. The MTD was defined as the highest dose at which 0 or 1 of 3 to 6 patients, respectively, experienced DLT during the first 3 weeks of treatment.

Detailed description:
The study consisted of a screening phase (maximum length of 21-day), a treatment phase with 21-day treatment cycles and a 30-day follow-up visit after the last dose of study medication.

The cut-off date for study part 1 was when last participant completed the first treatment cycle and the subsequent 30 days follow-up.

The cut off date for study part 2 was when all participants experienced disease progression, unacceptable toxicity, consent withdrawal or the last participant had completed 26 weeks or 6 cycles on study treatment, whichever came first.

Participants could continue to be treated on study as long as they were benefiting from study treatment and had not met study withdrawal criteria. After withdrawal from study treatment, further treatment, if any, was at the discretion of the Investigator.

Arms: arm 1: Cabazitaxel and gemcitabine on Day 1 then gemcitabine alone on Day 8 every 3 weeks until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision.

On Day 1, cabazitaxel was given either first followed by gemcitabine (part 1a) or after gemcitabine with 1 hour gap between the two infusions (part 1b). Required premedication with antihistamine, corticosteroid and H2 antagonist was administered intravenously 30 minutes before each dose of cabazitaxel.
Interventions: intervention 1: cabazitaxel intervention 2: gemcitabine
Intervention descriptions: intervention 1: Pharmaceutical form: 60 mg/1.5 ml concentrate solution for infusion

Route of administration: Intravenous infusion over 60 minutes

Dosage:

* Study part 1: 15, 20 or 25 mg/m\^2 according to pre-defined dose escalation schedule
* Study part 2: MTD as determined in Study part 1 intervention 2: Pharmaceutical form: According to United States Package Insert (USPI)

Route of administration: Intravenous infusion over 30 minutes

Dosage:

* Study part 1: 700, 900 or 1000 mg/m\^2 according to pre-defined dose escalation schedule
* Study part 2: MTD as determined in Study part 1.

Protocol documents: