A Phase I Study of Aflibercept Plus FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) in Chinese Patients With Advanced Solid Malignancies

Study Overview
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Brief Summary
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Primary Objective: To assess the safety and pharmacokinetics preliminarily of the dose of intravenous (IV) aflibercept used in western studies in combination with FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) given intravenously every 2 weeks in Chinese patients with solid tumors. Secondary Objectives: To make a preliminary assessment of antitumor effects of the combination of FOLFIRI plus aflibercept in patients with measurable disease (RECIST 1.1). To evaluate the immunogenicity of IV aflibercept.

Detailed Description
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Total duration of the study per patient is in the range of 17 to 29 weeks. This trial is being conducted in China, where the INN designation for the study molecule is aflibercept and this term is therefore used throughout the synopsis. In the US, the US proper name is ziv-aflibercept.

Official Title
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A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Aflibercept in Combination With FOLFIRI Administrated Every 2 Weeks in Chinese Patients With Advanced Solid Malignancies

Conditions
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Neoplasm Malignant

Intervention / Treatment
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* Drug: Aflibercept AVE0005
* Drug: Leucovorin
* Drug: Irinotecan
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which FOLFIRI (Irinotecan, 5-Fluorouracil, and Leucovorin) treatment is appropriate Exclusion criteria: Treatment with chemotherapy, hormonal therapy, radiotherapy, surgery, or an investigational agent within 28 days Eastern Cooperative Oncology Group (ECOG) >1 Need for a major surgical procedure or radiation therapy during the study Diagnosis of squamous-cell lung cancer Cumulative radiation therapy to > 25% of the total bone marrow History of brain metastases Inadequate organ and bone marrow function Uncontrolled hypertension Evidence of clinically significant bleeding diathesis or underlying coagulopathy Prior FOLFIRI treatment but have not been appropriate for safety reasons Patients with known Gilbert's syndrome 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>aflibercept IV infusion for 1 hour followed by FOLFIRI IV infusion every 2 weeks | Drug: Aflibercept AVE0005<br>* Pharmaceutical form:Solution for infusion Route of administration: Intravenous<br>Drug: Leucovorin<br>* Pharmaceutical form:Solution for infusion Route of administration: Intravenous<br>Drug: Irinotecan<br>* Pharmaceutical form:Solution for infusion Route of administration: Intravenous<br>Drug: 5-Fluorouracil<br>* Pharmaceutical form:Solution for infusion Route of administration: Intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with standard safety assessments (adverse events and laboratory tests) |  | Up to last treatment + 30 days | 
| Pharmacokinetics: Assessment of plasma concentrations of aflibercept, CPT-11 (irinotecan) and Fluorouracil (5-FU) |  | Up to last aflibercept administration + 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity assessment - overall response rate |  | Up to 17 Weeks | 
| Anti-tumor activity assessment - duration response |  | Up to 17 Weeks | 
| Anti-aflibercept antibody detection |  | Up to last aflibercept administration + 90 days |