An Open-label, Dose Escalation, Safety and Pharmacokinetics Phase 1 Study With AVE8062 Administered as a 30-minute Intravenous Infusion Every 3 Weeks in Patients With Advanced Solid Tumors.
Overview
- Phase
- Phase 1
- Intervention
- ombrabulin (AVE8062)
- Conditions
- Solid Tumor
- Sponsor
- Sanofi
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- Dose limiting toxicity at Cycle 1
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Primary objective: To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of AVE8062 administered every 3 weeks in patients with advanced solid tumors.
Secondary objectives:
- To assess the overall safety profile of the drug.
- To characterize the pharmacokinetic profile of AVE8062 and its active metabolite RPR 258063.
- To evaluate anti-tumor activity of the drug.
Detailed Description
The duration of the study for each patient will include an up to 4-week screening phase, 21-day study treatment cycles, an end of treatment visit and a follow-up period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Advanced solid tumor that has become refractory to conventional treatment or for which no standard therapy exists.
- •Patients with signed and dated Institutional Review Board (IRB)-approved patient informed consent form (ICF) prior to enrollment in the study.
Exclusion Criteria
- •Eastern Cooperative Oncology Group performance status \> or =
- •Life expectancy of less than 12 weeks.
- •Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study.
- •Absence of histologically or cytologically proven cancer.
- •Male patients who do not agree with contraception. Absence of negative serum/urinary pregnancy test within the 7 days prior to the enrollment in the study for female patients with childbearing potential. Patients must be post-menopausal, surgically sterile, or using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator).
- •Washout period of less than 28 days from prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy) or any investigational treatment, except for nitrosoureas, mitomycin which may not be used up to 42 days prior to the first cycle. No washout period is required for hormonal therapy, however, it must be discontinued before the first cycle.
- •Not recovered from all previous therapies (radiation, surgery, and medications). Adverse events related to previous therapies must be National Cancer Institute Common Terminology Criteria grade \< or = 1 (or alopecia \< or = grade 2) at screening or returned to the subject's baseline prior to their most recent previous therapy.
- •Symptomatic brain metastases and carcinomatous leptomeningitis.
- •Other serious illness or medical conditions:
- •Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
Arms & Interventions
1
Level 1: 15.5 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 2: 25 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 3: 35 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 4: 50 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal
Intervention: ombrabulin (AVE8062)
Outcomes
Primary Outcomes
Dose limiting toxicity at Cycle 1
Time Frame: 21 days
Secondary Outcomes
- Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities(all cycles)
- Pharmacokinetic parameters of AVE8062: Cmax, AUC, CL, Vss, and t1/2(Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles)
- Pharmacokinetic parameters of AVE8062's active metabolite RPR258063: Cmax, AUC, t1/2, and Metabolic ratio(Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles)
- Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors in evaluable patients(from patient informed consent to end of treatment)