Clinical trial NCT01907685: Dose Escalation, Safety and Pharmacokinetic Study of AVE8062 Combined With Docetaxel in Patients With Advanced Solid Tumors
Official title: An Open Label, Dose Escalation, Safety and Pharmacokinetic Phase 1 Study With AVE8062 Administered as a 30 Minutes Intravenous Infusion Followed by Docetaxel Administered as an 1 Hour Intravenous Infusion 24 Hours-Apart Every 3 Weeks in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Neoplastic Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-07-25
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: 3 weeks (cycle 1)
Secondary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: Up to disease progression or unacceptable toxicity or study discontinuation criteria (median treatment of 4 cycles)
measure: Plasma concentration of AVE8062 and its metabolite
timeFrame: 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)
measure: Plasma concentration of docetaxel
timeFrame: 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)
measure: Response evaluation criteria in solid tumors (RECIST) defined objective response
timeFrame: Up to disease progression or unacceptable toxicity or study discontinuation criteria (median treatment of 4 cycles)
measure: 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
timeFrame: End of treatment or until disease progression or unacceptable toxicity or study discontinuation criteria
Other outcomes:
Locations:
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Eskens FA, Tresca P, Tosi D, Van Doorn L, Fontaine H, Van der Gaast A, Veyrat-Follet C, Oprea C, Hospitel M, Dieras V. A phase I pharmacokinetic study of the vascular disrupting agent ombrabulin (AVE8062) and docetaxel in advanced solid tumours. Br J Cancer. 2014 Apr 29;110(9):2170-7. doi: 10.1038/bjc.2014.137. Epub 2014 Apr 8.