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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Sanofi
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01661270
First received: August 7, 2012
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

Primary Objective:

To evaluate the improvement in progression-free survival of aflibercept versus placebo in patients with metastatic colorectal cancer treated with FOLFIRI as second-line treatment for metastatic disease.

Secondary Objectives:

To compare the overall survival in the 2 treatment arms. To compare the overall response rate in the 2 treatment arms. To assess the safety profile of the 2 treatment arms. To assess immunogenicity of IV aflibercept in selected centers.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: Aflibercept AVE0005
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multinational, Randomized, Double-Blind Study of Aflibercept Versus Placebo With Irinotecan/ 5-FU Combination (FOLFIRI) in Patients With Metastatic Colorectal Cancer (MCRC) After Failure of an Oxaliplatin Based Regimen

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 7 months (the average) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 14 months (the average) ] [ Designated as safety issue: No ]
  • Overall Response Rate [ Time Frame: 7 months (the average) ] [ Designated as safety issue: No ]
  • Assess Immunogenicity of IV Aflibercept Patients [ Time Frame: Up to 90 days after last aflibercept/placebo administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: July 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aflibercept
One (1) hour intravenous (IV) on day 1 of each cycle, every 2 weeks in combination with FOLFIRI (irinotecan, 5- Fluorouracil and leucovorin) regimen
Drug: Aflibercept AVE0005
Pharmaceutical form:Concentrate for Solution for infusion Route of administration: Intravenous
Placebo Comparator: Placebo
One (1) hour intravenous(IV) on Day 1 of each cycle, every 2 weeks in combination with FOLFIRI (irinotecan, 5-Fluorouracil and leucovorin) regimen
Drug: Placebo
Pharmaceutical form:Concentrate for Solution for infusion Route of administration: Intravenous

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Histological or cytological proven adenocarcinoma of the colon or rectum.
  • Metastatic disease that is 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. Patients who relapse within 6 months of completion of oxaliplatin based adjuvant chemotherapy are 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.
  • Adverse events (with exception of alopecia, peripheral sensory neuropathy grade ≤ 2 and those listed in specific exclusion criteria) from any prior anticancer therapy of grade >1 (National Cancer Institute Common terminology Criteria [NCI CTCAE] v.3.0) at the time of 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 patient has been disease free for > 5 years are 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, 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.
  • Patients who had or are having high dose aspirin or NSAIDS (non steroidal anti-inflammatory agents) or high steroids within 4 weeks prior to randomization. The definition of "high dose" will 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. Patients with reproductive (M/F) who do 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/24h.
  • Patients on anticoagulant therapy with unstable dose of warfarin and/or having an out-of-therapeutic range 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 are CYP3A4 inducers (phenytoin, phenobarbital, carbamazepine), unless discontinued >7 days.
  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01661270

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
China
Investigational Site Number 156001 Active, not recruiting
Beijing, China, 100142
Investigational Site Number 156003 Active, not recruiting
Beijing, China, 100071
Investigational Site Number 156002 Active, not recruiting
Beijing, China, 100210
Investigational Site Number 156004 Active, not recruiting
Beijing, China, 100853
Investigational Site Number 156016 Active, not recruiting
Chengdu, China, 610041
Investigational Site Number 156020 Active, not recruiting
Chongqing, China, 400038
Investigational Site Number 156021 Active, not recruiting
Fuzhou, China, 350014
Investigational Site Number 156008 Active, not recruiting
Guangzhou, China, 510060
Investigational Site Number 156009 Active, not recruiting
Hangzhou, China, 310016
Investigational Site Number 156010 Active, not recruiting
Hangzhou, China, 310003
Investigational Site Number 156011 Active, not recruiting
Hangzhou, China, 310009
Investigational Site Number 156015 Active, not recruiting
Harbin, China, 150081
Investigational Site Number 156013 Active, not recruiting
Nanjing, China, 210029
Investigational Site Number 156012 Active, not recruiting
Nanjing, China, 210002
Investigational Site Number 156006 Active, not recruiting
Shanghai, China, 200032
Investigational Site Number 156007 Active, not recruiting
Shanghai, China, 200032
Investigational Site Number 156014 Active, not recruiting
Shenyang, China, 110001
Investigational Site Number 156005 Active, not recruiting
Tianjin, China, 300060
Investigational Site Number 156019 Active, not recruiting
Wuhan, China, 430022
Investigational Site Number 156018 Recruiting
Wuhan, China, 430030
Investigational Site Number 156017 Active, not recruiting
Xi'An, China, 710032
Hong Kong
Investigational Site Number 344002 Active, not recruiting
Hong Kong, Hong Kong
Investigational Site Number 344001 Active, not recruiting
Shatin, Nt, Hong Kong
Japan
Investigational Site Number 392006 Active, not recruiting
Amagasaki-Shi, Japan
Investigational Site Number 392003 Active, not recruiting
Bunkyo-Ku, Japan
Investigational Site Number 392004 Completed
Bunkyo-Ku, Japan
Investigational Site Number 392007 Active, not recruiting
Chuo-Ku, Kumamoto-Shi, Japan
Investigational Site Number 392009 Active, not recruiting
Gifu-Shi, Japan
Investigational Site Number 392002 Active, not recruiting
Kitaadachi-Gun, Japan
Investigational Site Number 392001 Active, not recruiting
Kobe-Shi, Japan
Investigational Site Number 392005 Active, not recruiting
Kochi-Shi, Japan
Investigational Site Number 392008 Active, not recruiting
Nagakute-Shi, Japan
Investigational Site Number 392010 Active, not recruiting
Takatsuki-Shi, Japan
Singapore
Investigational Site Number 702001 Active, not recruiting
Singapore, Singapore, 169610
Investigational Site Number 702002 Active, not recruiting
Singapore, Singapore, 119228
Taiwan
Investigational Site Number 158003 Active, not recruiting
Taipai, Taiwan, 10043
Investigational Site Number 158002 Active, not recruiting
Taipei, Taiwan
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01661270     History of Changes
Other Study ID Numbers: EFC11338, U1111-1115-7227
Study First Received: August 7, 2012
Last Updated: September 9, 2014
Health Authority: China: Ethics Committee

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014