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Colorectal Cancer MetastaticPhase 3AFLAMENCT01661270

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

A Phase 3 study testing Aflibercept in people with Colorectal Cancer Metastatic, run by Sanofi at 37 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer Metastatic
What is being tested?
Aflibercept
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
332 participants
Where
37 sitesin 5 countries
Study dates
Jul 2012to Jul 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.

Trial locations and contacts

37 sites in 5 countries.

37 sites in 5 countries

China21 sites

  • Investigational Site Number 156003

    Beijing, 100071

  • Investigational Site Number 156001

    Beijing, 100142

  • Investigational Site Number 156002

    Beijing, 100210

  • Investigational Site Number 156004

    Beijing, 100853

  • Investigational Site Number 156016

    Chengdu, 610041

  • Investigational Site Number 156020

    Chongqing, 400038

  • Investigational Site Number 156021

    Fuzhou, 350014

  • Investigational Site Number 156008

    Guangzhou, 510060

  • Investigational Site Number 156010

    Hangzhou, 310003

  • Investigational Site Number 156011

    Hangzhou, 310009

  • Investigational Site Number 156009

    Hangzhou, 310016

  • Investigational Site Number 156015

    Harbin, 150081

  • Investigational Site Number 156012

    Nanjing, 210002

  • Investigational Site Number 156013

    Nanjing, 210029

  • Investigational Site Number 156006

    Shanghai, 200032

  • Investigational Site Number 156007

    Shanghai, 200032

  • Investigational Site Number 156014

    Shenyang, 110001

  • Investigational Site Number 156005

    Tianjin, 300060

  • Investigational Site Number 156019

    Wuhan, 430022

  • Investigational Site Number 156018

    Wuhan, 430030

  • Investigational Site Number 156017

    Xi'an, 710032

Other trials in China

Japan10 sites

  • Investigational Site Number 392006

    Amagasaki-Shi

  • Investigational Site Number 392003

    Bunkyō City

  • Investigational Site Number 392004

    Bunkyō City

  • Investigational Site Number 392009

    Gifu

  • Investigational Site Number 392002

    Kitaadachi-Gun

  • Investigational Site Number 392001

    Kobe

  • Investigational Site Number 392005

    Kochi

  • Investigational Site Number 392007

    Kumamoto

  • Investigational Site Number 392008

    Nagakute-Shi

  • Investigational Site Number 392010

    Takatsuki-Shi

Other trials in Japan

Hong Kong2 sites

  • Investigational Site Number 344002

    Hong Kong

  • Investigational Site Number 344001

    Shatin, Nt

Other trials in Hong Kong

Singapore2 sites

  • Investigational Site Number 702002

    Singapore, 119228

  • Investigational Site Number 702001

    Singapore, 169610

Other trials in Singapore

Taiwan2 sites

  • Investigational Site Number 158003

    Taipai, 10043

  • Investigational Site Number 158002

    Taipei

Other trials in Taiwan

About this study

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

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.

Read the 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.

Being tested
Aflibercept, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfliberceptDrug

    Also called AVE0005, Zaltrap

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

  • PlaceboDrug

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

Study groups in NCT01661270
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo
AfliberceptExperimentalAflibercept 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.
Receives: Drug: Aflibercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 26.7 months

Secondary outcomes (2)

  1. Overall Survival (OS)

    OS was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the earliest between the last date of the participants was known to be alive and the study cut-off date. Analysis was performed by Kaplan-Meier method.

    Measured: 31.6 months

  2. Percentage of Participants With Objective Response

    Objective response rate was defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR), as assessed by Investigators and the IRC according to RECIST 1.0 criteria, relative to the total number of participants in the relevant analysis population. Complete Response (CR): disappearance of all target and non-target lesions and no new lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, the disappearance of all target lesions but persistence of 1 or more non-target lesions not qualifying for either CR or progressive disease (PD) and no new lesions.

    Measured: 26.6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionOct 2014
  4. Study completionJul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
332 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01661270
Sponsor's protocol ID
EFC11338
Other IDs
U1111-1115-7227
Acronym
AFLAME
Status last verified
Aug 2016
First submitted
7 Aug 2012
Last updated
18 Oct 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30117334

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aflibercept in people with Colorectal Cancer Metastatic, run by Sanofi at 37 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in China, Japan, Hong Kong, Singapore, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: 26.7 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01661270, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2016.

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