Study of Aflibercept And Modified FOLFOX6 As First-Line Treatment In Patients With Metastatic Colorectal Cancer - Clinical Trial for Colorectal Neoplasms | NCT00851084

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

aflibercept

oxaliplatin

5-FU

Folinic Acid

About this trial

This is an interventional treatment trial for Colorectal Neoplasms focused on measuring Angiogenesis, Colon cancer, Rectal cancer, Oxaliplatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

mFOLFOX6 only

mFOLFOX6 + aflibercept

Arm Description

modified FOLFOX6 chemotherapy regimen

modified FOLFOX6 chemotherapy regimen in combination with aflibercept

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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).

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).

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.

Immunogenicity of Intravenous (IV) Aflibercept

The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.

Full Information

NCT ID

NCT00851084

First Posted

February 24, 2009

Last Updated

May 4, 2016

Sponsor

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT00851084

Brief Title

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

Acronym

AFFIRM

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasms, Neoplasm Metastasis

Keywords

Angiogenesis, Colon cancer, Rectal cancer, Oxaliplatin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

268 (Actual)

8. Arms, Groups, and Interventions

Arm Title

mFOLFOX6 only

Arm Type

Active Comparator

Arm Description

modified FOLFOX6 chemotherapy regimen

Arm Title

mFOLFOX6 + aflibercept

Arm Type

Experimental

Arm Description

modified FOLFOX6 chemotherapy regimen in combination with aflibercept

Intervention Type

Drug

Intervention Name(s)

aflibercept

Other Intervention Name(s)

ZALTRAP™, AVE0005

Intervention Description

administration: IV infusion

Intervention Type

Drug

Intervention Name(s)

oxaliplatin

Intervention Description

administration: IV infusion

Intervention Type

Drug

Intervention Name(s)

5-FU

Intervention Description

administration: IV infusion

Intervention Type

Drug

Intervention Name(s)

Folinic Acid

Intervention Description

administration: IV infusion

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS) Rate at 12 Months

Description

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.

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

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.

Time Frame

From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Title

Overall Objective Response Rate (ORR)

Description

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).

Time Frame

From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Title

Overall Survival (OS)

Description

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).

Time Frame

From the date of the first randomization until the study data cut-off date, 14 April 2011 (approximately 26 months)

Title

Number of Participants With Treatment-emergent Adverse Events (TEAE)

Description

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.

Time Frame

From the date of the first randomization up to 30 days after the treatment discontinuation or until TEAE was resolved or stabilized

Title

Immunogenicity of Intravenous (IV) Aflibercept

Description

The antidrug antibody (ADA) assay was evaluated for participants receiving aflibercept.

Time Frame

Any time post baseline and 90 days after the last infusion of aflibercept, according to baseline status

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Histologically proven adenocarcinoma of the colon or the rectum Metastatic disease not amenable to potentially curative treatment Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John Zalcberg, MD

Organizational Affiliation

Peter Mc Callum Cancer Centre, Melbourne, Australia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sanofi-Aventis Investigational Site Number 036004

City

Douglas

ZIP/Postal Code

4814

Country

Australia

Facility Name

Sanofi-Aventis Investigational Site Number 036001

City

Hunter Region Mail Centre

ZIP/Postal Code

2310

Country

Australia

Facility Name

Sanofi-Aventis Investigational Site Number 036003

City

Hunter Region Mail Centre

ZIP/Postal Code

2310

Country

Australia

Facility Name

Sanofi-Aventis Investigational Site Number 276003

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276007

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276001

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276006

City

Homberg

ZIP/Postal Code

66421

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276004

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276002

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 276005

City

Recklinghausen

ZIP/Postal Code

45659

Country

Germany

Facility Name

Sanofi-Aventis Investigational Site Number 380005

City

Bari

ZIP/Postal Code

70126

Country

Italy

Facility Name

Sanofi-Aventis Investigational Site Number 380001

City

Firenze

ZIP/Postal Code

50141

Country

Italy

Facility Name

Sanofi-Aventis Investigational Site Number 380002

City

Milano

ZIP/Postal Code

20121

Country

Italy

Facility Name

Sanofi-Aventis Investigational Site Number 380003

City

Taormina

ZIP/Postal Code

98039

Country

Italy

Facility Name

Sanofi-Aventis Investigational Site Number 380004

City

Torino

ZIP/Postal Code

10126

Country

Italy

Facility Name

Sanofi-Aventis Investigational Site Number 410003

City

Busan

ZIP/Postal Code

614-735

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410004

City

Cheongju

ZIP/Postal Code

361-711

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410005

City

Daegu

ZIP/Postal Code

700-721

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410002

City

Daejeon

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410007

City

Goyang-Si, Gyeonggi-Do

ZIP/Postal Code

410-769

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410006

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410001

City

Seoul

ZIP/Postal Code

152-703

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 410008

City

Ulsan

ZIP/Postal Code

682-714

Country

Korea, Republic of

Facility Name

Sanofi-Aventis Investigational Site Number 643002

City

Pyatigorsk

ZIP/Postal Code

357500

Country

Russian Federation

Facility Name

Sanofi-Aventis Investigational Site Number 643005

City

Saint-Petersburg

ZIP/Postal Code

197758

Country

Russian Federation

Facility Name

Sanofi-Aventis Investigational Site Number 643001

City

Sochi

ZIP/Postal Code

354057

Country

Russian Federation

Facility Name

Sanofi-Aventis Investigational Site Number 724005

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 724004

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 724001

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 724002

City

Sabadell

ZIP/Postal Code

08208

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 724007

City

Santiago De Compostela

ZIP/Postal Code

15706

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 724003

City

Valencia

ZIP/Postal Code

46009

Country

Spain

Facility Name

Sanofi-Aventis Investigational Site Number 826004

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Sanofi-Aventis Investigational Site Number 826001

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Sanofi-Aventis Investigational Site Number 826002

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

Sanofi-Aventis Investigational Site Number 826003

City

Slough

ZIP/Postal Code

SL2 4HL

Country

United Kingdom

Facility Name

Sanofi-Aventis Investigational Site Number 826005

City

Southampton

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27091810

Citation

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.

Results Reference

result

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

Colorectal Neoplasms, Neoplasm Metastasis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial