Overview

Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor

Status:
Terminated
Trial end date:
2011-10-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Sanofi
Treatments:
Gemcitabine
Criteria
Inclusion criteria:

- Histologically or cytologically confirmed advanced solid malignancy that is metastatic
or unresectable, and for which standard curative measures do not exist.

Exclusion criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) > or =2

- Anticipation of need for a major surgical procedure or radiation therapy during the
study treatment

- Absence of completion of all prior chemotherapy, biological therapy, targeted
non-cytotoxic therapy > or = 3 weeks; and radiotherapy > or = 4 weeks prior to
registration. For part 2 only, prior treatment with radiotherapy, chemoembolization
therapy, or cryotherapy is allowed if these therapies are not directed to the areas of
measurable disease being used for the purposes of this protocol. (4 weeks of washout
period is required prior to start the treatment in Part 2)

- Concurrent treatment in another clinical trial or with any other cancer therapy or
patients planning to receive these treatments during the study

- Other concurrent serious illness or medical condition, including active infection or
human immunodeficiency virus (HIV) disease

- History of any other malignancy with the exception of adequately treated basal cell or
squamous cell skin cancer, or in situ carcinoma of the cervix uteri

- Patients without resolution of all clinically significant toxic effects (excluding
alopecia) of any prior therapy to grade < or = 1 by National Cancer Institute's Common
Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0 or to within the
limits listed in the specific inclusion/exclusion criteria

- Other severe acute or chronic medical or psychiatric condition, or significant
laboratory abnormality requiring further investigation that may cause undue risk for
the patient's safety, inhibit protocol participation, or interfere with interpretation
of study results, and in the judgment of the investigator would make the patient
inappropriate for entry into this study

- Symptomatic brain metastases or leptomeningeal disease. Patients with asymptomatic or
stable brain metastases are allowed

- Women of childbearing potential not protected by highly effective contraceptive method
of birth control. All patients of childbearing potential that do not have a negative
pregnancy test within the 7 days prior to registration

- Patients who are pregnant or breastfeeding

- For part 2, absence of measurable disease as defined by the most current version of
the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. For the Part 1
component, patients with non-measurable disease are accepted

- Inadequate bone marrow or liver or renal organ function

- Any condition which is considered a contraindication to gemcitabine in the local
labelling

- Prior treatment with cabazitaxel within the last 2 years

- History of severe hypersensitivity grade 3 or 4 to taxanes, Polysorbate-80, or to
compounds with similar chemical structures

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