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

NCT ID: NCT01661270

Last Updated: 2016-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 332 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-07-31

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.

Detailed Description

Screening occurred from signed informed consent to randomization (up to 21 days). A treatment cycle was defined as a 2 week-period. All participants were followed during the study treatment and follow-up period until death or study cut off date, which ever comes first.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Aflibercept

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.

Group Type: EXPERIMENTAL

Aflibercept

Intervention Type: DRUG

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

Interventions

Aflibercept

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

AVE0005; Zaltrap

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Participants on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range international normalized ratio (INR) (>3) within 4 weeks prior to randomization.
• Evidence of clinically significant bleeding diathesis or underlying coagulopathy.
• Known dihydropyrimidine dehydrogenase deficiency.
• Predisposing colonic or small bowel disorder in which the symptoms were uncontrolled as indicated by baseline of > 3 loose stools daily.
• Prior history of chronic enteropathy, inflammatory enteropathy, chronic diarrhea, unresolved bowel obstruction/sub-obstruction, more than hemicolectomy, extensive small intestine resection with chronic diarrhea.
• History of anaphylaxis or known intolerance to atropine sulphate or loperamide or appropriate antiemetics to be administered in conjunction with FOLFIRI.
• Treatment with concomitant anticonvulsant agents that were cytochrome P450 3A4 (CYP3A4) inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued > 7 days.
• Participants with known Gilbert's syndrome.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 156003

Beijing, , China

Investigational Site Number 156001

Beijing, , China

Investigational Site Number 156002

Beijing, , China

Investigational Site Number 156004

Beijing, , China

Investigational Site Number 156016

Chengdu, , China

Investigational Site Number 156020

Chongqing, , China

Investigational Site Number 156021

Fuzhou, , China

Investigational Site Number 156008

Guangzhou, , China

Investigational Site Number 156010

Hangzhou, , China

Investigational Site Number 156011

Hangzhou, , China

Investigational Site Number 156009

Hangzhou, , China

Investigational Site Number 156015

Harbin, , China

Investigational Site Number 156012

Nanjing, , China

Investigational Site Number 156013

Nanjing, , China

Investigational Site Number 156006

Shanghai, , China

Investigational Site Number 156007

Shanghai, , China

Investigational Site Number 156014

Shenyang, , China

Investigational Site Number 156005

Tianjin, , China

Investigational Site Number 156019

Wuhan, , China

Investigational Site Number 156018

Wuhan, , China

Investigational Site Number 156017

Xi'an, , China

Investigational Site Number 344002

Hong Kong, , Hong Kong

Investigational Site Number 344001

Shatin, Nt, , Hong Kong

Investigational Site Number 392006

Amagasaki-Shi, , Japan

Investigational Site Number 392003

Bunkyō City, , Japan

Investigational Site Number 392004

Bunkyō City, , Japan

Investigational Site Number 392009

Gifu, , Japan

Investigational Site Number 392002

Kitaadachi-Gun, , Japan

Investigational Site Number 392001

Kobe, , Japan

Investigational Site Number 392005

Kochi, , Japan

Investigational Site Number 392007

Kumamoto, , Japan

Investigational Site Number 392008

Nagakute-Shi, , Japan

Investigational Site Number 392010

Takatsuki-Shi, , Japan

Investigational Site Number 702002

Singapore, , Singapore

Investigational Site Number 702001

Singapore, , Singapore

Investigational Site Number 158003

Taipai, , Taiwan

Investigational Site Number 158002

Taipei, , Taiwan

Countries

China; Hong Kong; Japan; Singapore; Taiwan

References

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.

Reference Type: DERIVED

PMID: 30117334 (View on PubMed)

Other Identifiers

U1111-1115-7227

Identifier Type: OTHER

Identifier Source: secondary_id

EFC11338

Identifier Type: -

Identifier Source: org_study_id