A Study to Investigate the Disposition of Radio-labeled AVE8062 Compound Administered as a 30-minute IV Infusion to Patients With Advanced Solid Tumor

Study Overview
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Brief Summary
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Primary Objectives: To determine the excretion balance and systemic exposure of radioactivity after intravenous infusion of [14C]-AVE8062 to humans To determine the pharmacokinetics of AVE8062 and RPR258063 and their contribution to overall exposure To collect samples to determine the metabolic pathways of AVE8062 and identify the chemical structures of the main metabolites Secondary Objective: To assess the safety profile of the drug

Detailed Description
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The duration of the study for each patient will include approximately 4 weeks of a screening phase prior to first infusion of study drug, 21-day study treatment cycles and end of treatment visit. The patient can continue treatment until disease progression, unacceptable toxicity, or the patient's refusal of further treatment.

Official Title
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A Phase I, Open Label Study Investigating the Disposition of 25 mg/m² [14C]-AVE8062 (1.85 MBq, 50 µCi) Administered at Cycle 1 as a 30-minute Intravenous Infusion to Patients With Advanced Solid Tumors

Conditions
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Neoplasms, Malignant

Intervention / Treatment
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* Drug: Ombrabulin (AVE8062)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with advanced neoplastic disease that has become refractory to conventional treatment or for which no standard therapy exists. Age = or > 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Adequate hematological, hepatic and renal functions Exclusion criteria: Poor metabolizers for CYP2C19, CYP2C9, CYP2D6 and polymorphic UGTs will be excluded from the study The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C]-AVE8062<br>Single, 30 minute, intravenous infusion of 25 mg/m² of [14C]-AVE8062 containing 1.85 MBq (50µCi) at the first cycle, followed by subsequent administrations with non-radiolabelled AVE8062 in combination with cisplatin every 3 weeks, according to the investigator's judgment. | Drug: Ombrabulin (AVE8062)<br>* Pharmaceutical form:concentrate solution Route of administration: intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of radioactive dose excreted in urine, feces and expired air |  | 3 weeks (end of cycle 1) or 30 days after the first dose | 
| Concentration-time profiles and pharmacokinetic (PK) parameters of total radioactivity in whole blood and plasma; blood over plasma concentration ratios; Concentration-time profile and PK parameters of AVE8062 and RPR258063 in plasma |  | 3 weeks (end of cycle 1) or 30 days after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessment based on Adverse events reporting, laboratory tests according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTC) v3.0 grade scaling |  | 3 weeks (end of cycle 1) or 30 days after the first dose |