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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: Aflibercept AVE0005; Drug: Leucovorin; Drug: Irinotecan; Drug: 5-Fluorouracil

Detailed Description

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".

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100071
    • Investigational Site Number 156002
  • Guangzhou, China, 510060
    • Investigational Site Number 156001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cohort 1; aflibercept IV infusion for 1 hour followed by FOLFIRI IV infusion every 2 weeks

Drug: Aflibercept AVE0005; Pharmaceutical form:Solution for infusion Route of administration: Intravenous; Drug: Leucovorin; Pharmaceutical form:Solution for infusion Route of administration: Intravenous; Drug: Irinotecan; Pharmaceutical form:Solution for infusion Route of administration: Intravenous; Drug: 5-Fluorouracil; Pharmaceutical form:Solution for infusion Route of administration: Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 14, 2013
• First Submitted That Met QC Criteria: August 22, 2013
• First Posted (Estimate): August 29, 2013

Study Record Updates

• Last Update Posted (Estimate): January 7, 2015
• Last Update Submitted That Met QC Criteria: January 6, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Aflibercept
• Other Study ID Numbers: TCD11470; U1111-1115-7286 (Other Identifier: UTN)