An Open-label, Non-randomized, Dose Escalation, Safety and Pharmacokinetic Phase I Study of Ombrabulin (AVE8062) in Combination With Bevacizumab Administered by Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- Ombrabulin (AVE8062)
- Conditions
- Neoplasms, Malignant
- Sponsor
- Sanofi
- Enrollment
- 39
- Locations
- 4
- Primary Endpoint
- Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Primary Objective:
- To determine the maximum administered dose (MAD) and the maximum tolerated dose (MTD) of ombrabulin in combination with best tolerated dose of bevacizumab based on the incidence of related Dose Limiting Toxicities (DLTs).
Secondary Objectives:
- To assess the overall safety profile of the combination
- To characterize the pharmacokinetic (PK) profile of both ombrabulin and bevacizumab when given in combination
- To evaluate preliminary evidence of anti-tumor activity
- To assess the pharmacodynamic effect using (Dynamic Contrast Enhanced Ultra-Sound) DCE-US, measuring biomarkers
Detailed Description
The duration of the study for each patient will include an up to 28-day screening phase, 21-day study treatment cycles, an end of treatment visit with a follow-up period. Each patient will participate in only one dose group and will receive AVE8062 with bevacizumab every 3 weeks until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
AVE8062/ bevacizumab
The combination of ombrabulin and bevacizumab will be administered every 3 weeks according to the following schedule: One day 1, ombrabulin will be administered as a 30 minutes intravenous (i.v) infusion. Bevacizumab will be administered as a 30-90 minutes i.v. infusion 24 hours after the end of ombrabulin infusion on day 2.
Intervention: Ombrabulin (AVE8062)
AVE8062/ bevacizumab
The combination of ombrabulin and bevacizumab will be administered every 3 weeks according to the following schedule: One day 1, ombrabulin will be administered as a 30 minutes intravenous (i.v) infusion. Bevacizumab will be administered as a 30-90 minutes i.v. infusion 24 hours after the end of ombrabulin infusion on day 2.
Intervention: bevacizumab
Outcomes
Primary Outcomes
Incidence of Dose Limiting Toxicities (DLTs) that will define the MTD
Time Frame: 3 weeks
Secondary Outcomes
- Pharmacokinetic parameters of ombrabulin(6 weeks)
- Overall safety profile of the combination(up to a maximum follow-up of 1 year)
- Pharmacokinetic parameters of bevacizumab(6 weeks)
- Preliminary evidence of antitumor activity according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)(up to a maximum follow-up of 1 year)
- Pharmacodynamic effect (biomarkers)(cycle 1)