A Study of Aflibercept Versus Placebo With FOLFIRI in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin Chemotherapy

NCT01661270 | Completed Phase 3 Results DMC

• 2 other identifiers: EFC11338U1111-1115-7227
• Study Type: interventional
• Target: 332
• Locations: 5 countries
• Sites: 37

Brief Summary

Primary Objective: To evaluate the improvement in progression-free survival (PFS) of aflibercept versus placebo in participants with metastatic colorectal cancer treated with FOLFIRI as second-line treatment for metastatic disease. Secondary Objectives: To compare the overall survival (OS) in the 2 treatment arms. To compare the overall response rate (ORR) in the 2 treatment arms. To assess the safety profile of the 2 treatment arms. To assess immunogenicity of intravenous (IV) aflibercept in selected centers.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS was defined as the time interval from the date of randomization to the date of first observation of either tumor progression or death due to any cause. Tumor assessment was performed by Independent Review Committee (IRC) as per response evaluation criteria in solid tumors (RECIST) version 1.0. Progression was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study or absolute increase and at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was calculated by Kaplan-Meier estimates.

  26.7 months

Secondary Outcomes (2)

• Overall Survival (OS)

  31.6 months

• Percentage of Participants With Objective Response

  26.6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo for aflibercept intravenous (IV) infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.

Drug: Placebo

Aflibercept

EXPERIMENTAL

Aflibercept 4 mg/kg IV infusion on Day 1 of each cycle (1 cycle = 2 weeks) in combination with FOLFIRI regimen until disease progression, unacceptable toxicity or participant's refusal. FOLFIRI regimen: Irinotecan 180 mg/m\^2 IV infusion and leucovorin 400 mg/m\^2 IV infusion, 5-Fluorouracil IV bolus 400 mg/m\^2 followed by continuous IV infusion 2400 mg/m\^2.

Drug: Aflibercept

Interventions

Aflibercept DRUG

Pharmaceutical form: Concentrate for Solution for infusion; Route of administration: Intravenous

Also known as: AVE0005, Zaltrap

Aflibercept

Placebo DRUG

Pharmaceutical form: Concentrate for Solution for infusion; Route of administration: Intravenous

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological proven adenocarcinoma of the colon or rectum.
• Metastatic disease that was not amenable to potentially curative treatment.
• One and only one prior chemotherapeutic regimen for metastatic disease. This prior chemotherapy must be an oxaliplatin containing regimen. Participants who were relapsed within 6 months of completion of oxaliplatin based adjuvant chemotherapy were eligible.

You may not qualify if:

• Prior therapy with irinotecan.
• Eastern Cooperative Oncology Group (ECOG) performance status \>1.
• Less than 28 days elapsed from prior radiotherapy, from prior surgery and prior chemotherapy to the time of randomization. Less than 42 days elapsed from prior major surgery to the time to randomization.
• Age \<18 years.
• History of brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis or new evidence of brain or leptomeningeal disease.
• Other prior malignancy. Adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or any other cancer from which the participants had disease free for \> 5 years were allowed.
• Participation in another clinical trial with an investigational drug and any concurrent treatment with any investigational drug within 30 days prior to randomization.
• Any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association Functional Classification (NYHA) class III or IV congestive heart failure, stroke or transient ischemic attack.
• Any of the following within 3 months prior to randomization: treatment resistant peptic or duodenal ulcer disease, erosive oesophagitis or gastritis, grade 3 or 4 gastrointestinal bleeding/hemorrhage, gastrointestinal perforation/fistula, abdominal abscess, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
• Participants who had given high dose of aspirin or non steroidal anti-inflammatory agents (NSAIDS) or high steroids within 4 weeks prior to randomization. The definition of "high dose" was to be based on the investigator's judgment.
• Occurrence of deep vein thrombosis within 4 weeks, prior to randomization.
• Inadequate organ or bone marrow function.
• Pregnant or breast-feeding woman. Positive serum or urine pregnancy test prior to randomization. Participants with reproductive (M/F) who were not agree to use accepted and effective method of contraception during the study treatment period and for at least 6 months following completion of study treatment.
• Uncontrolled hypertension.
• Urine Protein: creatine ratio (UPCR) \>1 on morning spot urinalysis or proteinuria \> 500mg/24 hours.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (37)

Investigational Site Number 156003

Beijing, 100071, China

Location

Investigational Site Number 156001

Beijing, 100142, China

Location

Investigational Site Number 156002

Beijing, 100210, China

Location

Investigational Site Number 156004

Beijing, 100853, China

Location

Investigational Site Number 156016

Chengdu, 610041, China

Location

Investigational Site Number 156020

Chongqing, 400038, China

Location

Investigational Site Number 156021

Fuzhou, 350014, China

Location

Investigational Site Number 156008

Guangzhou, 510060, China

Location

Investigational Site Number 156010

Hangzhou, 310003, China

Location

Investigational Site Number 156011

Hangzhou, 310009, China

Location

Investigational Site Number 156009

Hangzhou, 310016, China

Location

Investigational Site Number 156015

Harbin, 150081, China

Location

Investigational Site Number 156012

Nanjing, 210002, China

Location

Investigational Site Number 156013

Nanjing, 210029, China

Location

Investigational Site Number 156006

Shanghai, 200032, China

Location

Investigational Site Number 156007

Shanghai, 200032, China

Location

Investigational Site Number 156014

Shenyang, 110001, China

Location

Investigational Site Number 156005

Tianjin, 300060, China

Location

Investigational Site Number 156019

Wuhan, 430022, China

Location

Investigational Site Number 156018

Wuhan, 430030, China

Location

Investigational Site Number 156017

Xi'an, 710032, China

Location

Investigational Site Number 344002

Hong Kong, Hong Kong

Location

Investigational Site Number 344001

Shatin, Nt, Hong Kong

Location

Investigational Site Number 392006

Amagasaki-Shi, Japan

Location

Investigational Site Number 392003

Bunkyō City, Japan

Location

Investigational Site Number 392004

Bunkyō City, Japan

Location

Investigational Site Number 392009

Gifu, Japan

Location

Investigational Site Number 392002

Kitaadachi-Gun, Japan

Location

Investigational Site Number 392001

Kobe, Japan

Location

Investigational Site Number 392005

Kochi, Japan

Location

Investigational Site Number 392007

Kumamoto, Japan

Location

Investigational Site Number 392008

Nagakute-Shi, Japan

Location

Investigational Site Number 392010

Takatsuki-Shi, Japan

Location

Investigational Site Number 702002

Singapore, 119228, Singapore

Location

Investigational Site Number 702001

Singapore, 169610, Singapore

Location

Investigational Site Number 158003

Taipai, 10043, Taiwan

Location

Investigational Site Number 158002

Taipei, Taiwan

Location

Related Publications (1)

• Li J, Xu R, Qin S, Liu T, Pan H, Xu J, Bi F, Lim R, Zhang S, Ba Y, Bai Y, Fan N, Tsuji A, Yeh KH, Ma B, Wei V, Shi D, Magherini E, Shen L. Aflibercept plus FOLFIRI in Asian patients with pretreated metastatic colorectal cancer: a randomized Phase III study. Future Oncol. 2018 Aug;14(20):2031-2044. doi: 10.2217/fon-2017-0669. Epub 2018 Aug 17.

  PMID: 30117334 DERIVED

MeSH Terms

Interventions

aflibercept

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: July 1, 2015
• Last Updated: October 18, 2016
• Results First Posted: November 26, 2015

Record last verified: 2016-08

Locations

HK (2); TW (2); SG (2); CN (21); JP (10)