Colorectal NeoplasmsPhase 2AFFIRMNCT00851084

Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer

A Phase 2 study testing aflibercept, oxaliplatin and 5-FU in people with Colorectal Neoplasms and Neoplasm Metastasis, run by Sanofi at 37 sites in 7 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

The primary objective of the study is to estimate the progression-free survival rate at 12 months for the two arms of the study. Secondary objectives include the evaluation of overall objective response rate to treatment, progression-free survival, overall survival, safety and documentation of potential immunogenicity… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Neoplasms, Neoplasm Metastasis
What is being tested?: aflibercept, oxaliplatin and 5-FU
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 268 participants
Where: 37 sitesin 7 countries
Study dates: Feb 2009to Jan 2012
Phase: Phase 2
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

Histologically proven adenocarcinoma of the colon or the rectum
Metastatic disease not amenable to potentially curative treatment

Who cannot join

Prior therapy for metastatic cancer of the colon or the rectum
Prior treatment with angiogenesis inhibitors
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial locations and contacts

37 sites in 7 countries.

Country

City, postcode or hospital

37 sites in 7 countries

South Korea8 sites

Sanofi-Aventis Investigational Site Number 410003
Busan, 614-735
Sanofi-Aventis Investigational Site Number 410004
Cheongju-si, 361-711
Sanofi-Aventis Investigational Site Number 410005
Daegu, 700-721
Sanofi-Aventis Investigational Site Number 410002
Daejeon
Sanofi-Aventis Investigational Site Number 410007
Goyang-Si, Gyeonggi-Do, 410-769
Sanofi-Aventis Investigational Site Number 410006
Seoul, 120-752
Sanofi-Aventis Investigational Site Number 410001
Seoul, 152-703
Sanofi-Aventis Investigational Site Number 410008
Ulsan, 682-714

Other trials in South Korea

Germany7 sites

Sanofi-Aventis Investigational Site Number 276003
Berlin, 13353
Sanofi-Aventis Investigational Site Number 276007
Dresden, 01307
Sanofi-Aventis Investigational Site Number 276001
Hanover, 30625
Sanofi-Aventis Investigational Site Number 276006
Homberg (Efze), 66421
Sanofi-Aventis Investigational Site Number 276004
Mannheim, 68167
Sanofi-Aventis Investigational Site Number 276002
Münster, 48149
Sanofi-Aventis Investigational Site Number 276005
Recklinghausen, 45659

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Spain6 sites

Sanofi-Aventis Investigational Site Number 724005
Barcelona, 08036
Sanofi-Aventis Investigational Site Number 724004
Madrid, 28007
Sanofi-Aventis Investigational Site Number 724001
Madrid, 28040
Sanofi-Aventis Investigational Site Number 724002
Sabadell, 08208
Sanofi-Aventis Investigational Site Number 724007
Santiago de Compostela, 15706
Sanofi-Aventis Investigational Site Number 724003
Valencia, 46009

Other trials in Spain

Italy5 sites

Sanofi-Aventis Investigational Site Number 380005
Bari, 70126
Sanofi-Aventis Investigational Site Number 380001
Florence, 50141
Sanofi-Aventis Investigational Site Number 380002
Milan, 20121
Sanofi-Aventis Investigational Site Number 380003
Taormina, 98039
Sanofi-Aventis Investigational Site Number 380004
Torino, 10126

Other trials in Italy

United Kingdom5 sites

Sanofi-Aventis Investigational Site Number 826004
Leeds, LS9 7TF
Sanofi-Aventis Investigational Site Number 826001
Leicester, LE1 5WW
Sanofi-Aventis Investigational Site Number 826002
Manchester, M20 4BX
Sanofi-Aventis Investigational Site Number 826003
Slough, SL2 4HL
Sanofi-Aventis Investigational Site Number 826005
Southampton, SO16 6YD

Other trials in United Kingdom

Australia3 sites

Sanofi-Aventis Investigational Site Number 036004
Douglas, 4814
Sanofi-Aventis Investigational Site Number 036001
Hunter Region Mail Centre, 2310
Sanofi-Aventis Investigational Site Number 036003
Hunter Region Mail Centre, 2310

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Russia3 sites

Sanofi-Aventis Investigational Site Number 643002
Pyatigorsk, 357500
Sanofi-Aventis Investigational Site Number 643005
Saint Petersburg, 197758
Sanofi-Aventis Investigational Site Number 643001
Sochi, 354057

Other trials in Russia

About this study

Official title: Randomized, Multinational, Study Of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer

The primary objective of the study is to estimate the progression-free survival rate at 12 months for the two arms of the study.

Secondary objectives include the evaluation of overall objective response rate to treatment, progression-free survival, overall survival, safety and documentation of potential immunogenicity of aflibercept.

This study was a non-comparative randomized trial and was not powered for a comparison of any of the efficacy endpoints.

Rather, the aim of the trial was to get, for all endpoints, an estimation of the efficacy and safety of aflibercept combined with a modified FOLFOX6 regimen. In such type of non-comparative randomized trial, the control FOLFOLX6 arm was intended to only act as a check on the similarity of the current patients to the historical controls with respect to clinical outcome when given FOLFOX6 treatment.

Conditions: Colorectal Neoplasms, Neoplasm Metastasis
Being tested: aflibercept, oxaliplatin, 5-FU, Folinic Acid
Keywords: Angiogenesis, Colon cancer, Rectal cancer, Oxaliplatin
Medical subject headings: Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Rectal Neoplasms

What participants receive

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

afliberceptDrug
Also called ZALTRAP™, AVE0005
administration: IV infusion
oxaliplatinDrug
administration: IV infusion
5-FUDrug
administration: IV infusion
Folinic AcidDrug
administration: IV infusion

Study groups in NCT00851084
Study group	Role	What they receive
mFOLFOX6 only	Active comparator	modified FOLFOX6 chemotherapy regimen Receives: Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid
mFOLFOX6 + aflibercept	Experimental	modified FOLFOX6 chemotherapy regimen in combination with aflibercept Receives: Drug: aflibercept; Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

What is being measured

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

Progression Free Survival (PFS) Rate at 12 Months
PFS rate at 12 months was defined as the percentage of patients alive without disease progression at 12 months after randomization. The primary efficacy analysis was based on assessment by the Independent Review Committee (IRC). The study was not powered for comparison of PFS rate at 12 months between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
Measured: 12 months

Secondary outcomes (5)

Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of tumor progression or death from any cause, whichever occurred first. PFS was based on tumor assessment by the Independent Review Committee (IRC). PFS was estimated from Kaplan-Meier Curves.
The study was not powered for comparison of PFS between the two arms (non-comparative, open-label study).
Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.
Measured: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Overall Objective Response Rate (ORR)
Summary of overall objective response rate based on tumor assessment by the Independent Review Committee (IRC) as per Response Evaluation Criteria in Solid Tumours (RECIST) criteria. ORR was defined as the proportion of patients with confirmed Complete Response (CR) or confirmed Partial Response (PR) relative to the total number of patients in the analysis population.
Per RECIST v 1.0 target lesions evaluation and assessed by tumor imaging: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
The study was not powered for comparison of ORR between the two arms (non-comparative, open-label study).
Measured: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. In absence of confirmation of death, survival time was censored at the earliest between the last date the patient was known to be alive and the study cutoff date.
The study was not powered for comparison of OS between the two arms (non-comparative, open-label study).
Measured: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Summary of treatment-emergent adverse events in the safety population. The National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 3.0 was used in this study to grade the severity of AEs.
Measured: From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Immunogenicity of Intravenous (IV) Aflibercept
The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.
Measured: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status

Timeline

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

Feb 2009Jan 2012

First posted25 Feb 2009 (estimated)
Study startFeb 2009
Primary completionApr 2011
Study completionJan 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
More trials run by SanofiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 268 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00851084
Sponsor's protocol ID: EFC10668
Other IDs: EudraCT 2008-004178-41
Acronym: AFFIRM
Status last verified: May 2016
First submitted: 24 Feb 2009
Last updated: 7 Jun 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Folprecht G, Pericay C, Saunders MP, Thomas A, Lopez Lopez R, Roh JK, Chistyakov V, Hohler T, Kim JS, Hofheinz RD, Ackland SP, Swinson D, Kopp M, Udovitsa D, Hall M, Iveson T, Vogel A, Zalcberg JR. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol. 2016 Jul;27(7):1273-9. doi: 10.1093/annonc/mdw176. Epub 2016 Apr 18.
PubMed 27091810

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized, Multinational, Study Of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT00851084
Acronym / sponsor ID: AFFIRM / EFC10668
Conditions: Colorectal Neoplasms, Neoplasm Metastasis
Keywords: Angiogenesis, Colon cancer, Rectal cancer, Oxaliplatin
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 268 participants (actual)
Lead sponsor: SanofiIndustry (pharma, biotech, devices)
Study start: Feb 2009
Primary completion: Apr 2011 (actual)
Study completion: Jan 2012 (actual)
First posted: 25 Feb 2009 (estimated)
Results: Posted 25 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary objective of the study is to estimate the progression-free survival rate at 12 months for the two arms of the study.

This study was a non-comparative randomized trial and was not powered for a comparison of any of the efficacy endpoints.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
mFOLFOX6 only	Active comparator	Drug: oxaliplatin, Drug: 5-FU, Drug: Folinic Acidmodified FOLFOX6 chemotherapy regimen
mFOLFOX6 + aflibercept	Experimental	Drug: aflibercept, Drug: oxaliplatin, Drug: 5-FU, Drug: Folinic Acidmodified FOLFOX6 chemotherapy regimen in combination with aflibercept

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Histologically proven adenocarcinoma of the colon or the rectum
Metastatic disease not amenable to potentially curative treatment

Key exclusion criteria (3 listed)

Prior therapy for metastatic cancer of the colon or the rectum
Prior treatment with angiogenesis inhibitors
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
afliberceptAlso: ZALTRAP™, AVE0005administration: IV infusion	Drug	mFOLFOX6 + aflibercept
oxaliplatinadministration: IV infusion	Drug	mFOLFOX6 + aflibercept, mFOLFOX6 only
5-FUadministration: IV infusion	Drug	mFOLFOX6 + aflibercept, mFOLFOX6 only
Folinic Acidadministration: IV infusion	Drug	mFOLFOX6 + aflibercept, mFOLFOX6 only

Primary outcome

Progression Free Survival (PFS) Rate at 12 Months
Time frame: 12 months
PFS rate at 12 months was defined as the percentage of patients alive without disease progression at 12 months after randomization. The primary efficacy analysis was based on assessment by the Independent Review Committee (IRC). The study was not powered for comparison of PFS rate at 12 months between the two arms (non-comparative, open-label study). Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0), as at least a 20 percent increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions.

5 secondary outcomes

Progression Free Survival (PFS)
Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Overall Objective Response Rate (ORR)
Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Overall Survival (OS)
Time frame: From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)
Number of Participants With Treatment-emergent Adverse Events (TEAE)
Time frame: From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized
Immunogenicity of Intravenous (IV) Aflibercept
Time frame: Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status

Results and safety

Results posted to the registry on 25 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
mFOLFOX6 Only	117	0
mFOLFOX6 + Aflibercept	119	0

Primary outcome: Progression Free Survival (PFS) Rate at 12 Months

Time frame: 12 months. Number (95% Confidence Interval). Unit: percentage of participants

Measure	mFOLFOX6 Only n = 111	mFOLFOX6 + Aflibercept n = 116
Value	21.2 (12.2 to 30.3)	25.8 (17.2 to 34.4)

Population analysed: Analyses of PFS rate was performed in the evaluable patient (EP) population as the primary analysis population. Overall, 9 patients from the randomized population were excluded from the EP population.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
mFOLFOX6 Only	32 of 116 (27.6%)	114 of 116 (98.3%)	Not reported
mFOLFOX6 + Aflibercept	55 of 119 (46.2%)	117 of 119 (98.3%)	Not reported

Limitations and caveats (from the sponsor): The overall survival (OS) data are severely limited due to the low number of events (\<50%) in both arms, therefore median OS cannot be accurately estimated due to limitations of available data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27091810Folprecht G, Pericay C, Saunders MP, Thomas A, Lopez Lopez R, Roh JK, Chistyakov V, Hohler T, Kim JS, Hofheinz RD, Ackland SP, Swinson D, Kopp M, Udovitsa D, Hall M, Iveson T, Vogel A, Zalcberg JR. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in first-line treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol. 2016 Jul;27(7):1273-9. doi: 10.1093/annonc/mdw176. Epub 2016 Apr 18.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

John Zalcberg, MD principal investigator

Peter Mc Callum Cancer Centre, Melbourne, Australia

37 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing aflibercept, oxaliplatin and 5-FU in people with Colorectal Neoplasms and Neoplasm Metastasis, run by Sanofi at 37 sites in 7 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 2 inclusion and 3 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 7 Jun 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 South Korea, Germany, Spain, Italy, United Kingdom and 2 more countries. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 25 Jun 2013). 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) Rate at 12 Months (time frame: 12 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 NCT00851084, 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 7 Jun 2016.