A Study of Intravenous Aflibercept With Docetaxel in Chinese Patients With Solid Tumors

Study Overview
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Brief Summary
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Primary Objective: To confirm the dose of aflibercept in western studies by assessing the dose-limiting toxicity (DLT) of intravenous (IV) aflibercept when administered in combination with docetaxel given intravenously every 3 weeks in Chinese patients with solid tumors. Secondary Objectives: To assess the safety profile of intravenous (IV) aflibercept when administered in combination with docetaxel To determine the pharmacokinetics of IV aflibercept and docetaxel when administered in combination To make a preliminary assessment of antitumor effects of the combination of docetaxel plus aflibercept in patients with evaluable disease To evaluate the immunogenicity of IV aflibercept To measure endogenous free Vascular Endothelial Growth Factor (VEGF)

Detailed Description
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The duration of screening, treatment, and follow-up are within 21 days, 3 weeks/cycle, and 90 days after the last aflibercept administration. Patients will be administered aflibercept in combination with docetaxel until when/if a definitive treatment discontinuation criterion is met such as progressive disease, unacceptable toxicity or patient refusal to continue.

Official Title
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A Phase I, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Aflibercept in Combination With Intravenous Docetaxel Administrated Every 3 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: Docetaxel (XRP6976)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Histologically or cytologically confirmed solid malignancy that metastatic or unresectable for which standard curative measures do not exist, but for which docetaxel treatment is appropriate. Exclusion criteria : Squamous histology/cytology lung cancer Need for a major surgical procedure or radiation therapy during the study Treatment with chemotherapy, hormonal therapy, radiotherapy, surgery, or an investigational agent within 28 days Cumulative radiation therapy to >25% of the total bone marrow History of brain metastases Eastern Cooperative Oncology Group(ECOG)>1 Prior docetaxel treatment but have not been appropriate for safety reasons Inadequate organ and bone marrow function Uncontrolled hypertension Evidence of clinically significant bleeding diathesis or underlying coagulopathy 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: Aflibercept/ docetaxel<br>Patients with advanced cancer will receive different doses of aflibercept in combination with approved dose of docetaxel. Aflibercept 4 or 6mg/kg over 1 hour IV immediately followed by Docetaxel 75mg/m2 IV over 1 hour on Day 1, every 3 weeks | Drug: Aflibercept (AVE0005)<br>* Pharmaceutical form: solution for infusion Route of administration: intravenous<br>Drug: Docetaxel (XRP6976)<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 |
| --- | --- | --- |
| Dose-Limiting Toxicity (DLT) |  | 3 weeks (cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities |  | Up to 30 days after last administration within a maximum follow up of 18 months | 
| Pharmacokinetic parameters of aflibercept |  | up to last aflibercept administration +90 days | 
| Pharmacokinetic parameters of docetaxel |  | cycle 1 | 
| Tumor response rate as calculated by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |  | up to a maximum follow-up of 18 months | 
| Immunogenicity of Aflibercept |  | up to last aflibercept administration+90 days | 
| Endogenous free VEGF |  | up to last aflibercept administration+30 days |