Advanced Neoplastic Disease
Conditions
Brief summary
Primary Objective: To determine the dose limiting toxicity (DLT), the maximum administered dose (MAD) and the maximum tolerated dose (MTD) of AVE8062 and docetaxel in combination administered sequentially on D1 & D2 respectively every 3 weeks in patients with advanced solid tumors. Secondary Objectives: * To define the overall safety profile of the combination. * To characterize the pharmacokinetic (PK) profile of AVE8062 and docetaxel when administered in combination. * To evaluate anti-tumor activity of the combination. * To evaluate potential predictive biomarkers. The study includes a tumoral pharmacogenomic sub-study conducted in a subset of sites. The objective to analyse a set of biological biomarkers in order to identify a potential predictive signature of efficacy for AVE8062 in combination with docetaxel.
Detailed description
The duration of study for each patient will include 4-week screening phase prior to first inclusion of study drug, 21-day study treatment cycles, end of treatment visit and follow-up phase. Each patient will be treated until disease progression, unacceptable toxicity or other study discontinuation criteria.
Interventions
DRUGAVE8062
Pharmaceutical form:Solution for infusion Route of administration: Intravenous
DRUGDocetaxel
Pharmaceutical form: solution for infusion Route of administration: Intravenous
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Advanced neoplastic disease (i.e metastatic or locally advanced disease) for which docetaxel-based regimen therapy is indicated such as breast, non-small cell lung and prostate cancer. * ECOG performance status of 0 to 1.
Exclusion criteria
* Concurrent treatment with any other anticancer therapy. * Patient with locally advanced or metastatic breast cancer who never received adjuvant chemotherapy. * Brain metastases and carcinomatous leptomeningitis. * Prior intensive chemotherapy with autologous stem cell rescue. * Patients who received a high cumulative dose of anthracycline (i.e doxorubicin \> 400mg/m2 or epirubicin \>750 mg/m2). * Impaired cardiovascular function. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | 3 weeks (cycle 1) |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants with Adverse Events | Up to disease progression or unacceptable toxicity or study discontinuation criteria (median treatment of 4 cycles) |
| Plasma concentration of AVE8062 and its metabolite | Before AVE8062 infusion, immediately prior to the end of AVE8062 infusion, 5, 10, 25, 45 and 60 minutes then 2, 4, 6, 8-10 and 24 hours post AVE8062 infusion (cycle 1) |
| Plasma concentration of docetaxel | Before docetaxel infusion (corresponding to 24 hours post AVE8062 infusion), 15 minutes before the end of docetaxel infusion, 15 and 45 minutes post docetaxel infusion (cycle 1) |
| Response evaluation criteria in solid tumors (RECIST) defined objective response | Up to disease progression or unacceptable toxicity or study discontinuation criteria (median treatment of 4 cycles) |
| Biomarkers expression profile of each patient in order to identify preliminary correlation with antitumor activity of the combination treatment in patients with available pre-treatment biopsy | End of treatment or until disease progression or unacceptable toxicity or study discontinuation criteria |
Outcome results
None listed