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

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

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)

Study Overview

• Status: Completed
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: Aflibercept (AVE0005); Drug: Docetaxel (XRP6976)

Detailed Description

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.

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

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510060
    • Sanofi-Aventis 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aflibercept/ docetaxel; 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); Pharmaceutical form: solution for infusion Route of administration: intravenous; Drug: Docetaxel (XRP6976); Pharmaceutical form: solution for infusion Route of administration: intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-Limiting Toxicity (DLT)	3 weeks (cycle 1)

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Huang Y, Zou BY, Zhao LP, Zhao HY, Zhao YY, Xue C, Zhang JW, Xu F, Chen LK, Liu JL, Hu ZH, Wu X, Zhang J, Ma YX, Wei CL, Ma Y, Zhang L. Phase I dose-escalation study of aflibercept plus docetaxel in nasopharyngeal carcinoma and other solid tumors. Future Oncol. 2014 Dec;10(16):2579-91. doi: 10.2217/fon.14.206.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): September 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: June 21, 2010
• First Submitted That Met QC Criteria: June 21, 2010
• First Posted (ESTIMATE): June 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 13, 2012
• Last Update Submitted That Met QC Criteria: January 12, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Docetaxel; Aflibercept
• Other Study ID Numbers: TCD11382; U1111-1116-5774 (OTHER: UTN)