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

NCT00851084 | Completed Phase 2 Results DMC

• 2 other identifiers: EFC10668EudraCT 2008-004178-41
• Study Type: interventional
• Target: 268
• Locations: 7 countries
• Sites: 37

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.

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Keywords

Angiogenesis; Colon cancer; Rectal cancer; Oxaliplatin

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  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)

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

• Overall Survival (OS)

  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)

  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

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

Study Arms (2)

mFOLFOX6 only

ACTIVE COMPARATOR

modified FOLFOX6 chemotherapy regimen

Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

mFOLFOX6 + aflibercept

EXPERIMENTAL

modified FOLFOX6 chemotherapy regimen in combination with aflibercept

Drug: aflibercept; Drug: oxaliplatin; Drug: 5-FU; Drug: Folinic Acid

Interventions

aflibercept DRUG

administration: IV infusion

Also known as: ZALTRAP™, AVE0005

mFOLFOX6 + aflibercept

oxaliplatin DRUG

administration: IV infusion

mFOLFOX6 + aflibercept; mFOLFOX6 only

5-FU DRUG

administration: IV infusion

mFOLFOX6 + aflibercept; mFOLFOX6 only

Folinic Acid DRUG

administration: IV infusion

mFOLFOX6 + aflibercept; mFOLFOX6 only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (37)

Sanofi-Aventis Investigational Site Number 036004

Douglas, 4814, Australia

Location

Sanofi-Aventis Investigational Site Number 036001

Hunter Region Mail Centre, 2310, Australia

Location

Sanofi-Aventis Investigational Site Number 036003

Hunter Region Mail Centre, 2310, Australia

Location

Sanofi-Aventis Investigational Site Number 276003

Berlin, 13353, Germany

Location

Sanofi-Aventis Investigational Site Number 276007

Dresden, 01307, Germany

Location

Sanofi-Aventis Investigational Site Number 276001

Hanover, 30625, Germany

Location

Sanofi-Aventis Investigational Site Number 276006

Homberg (Efze), 66421, Germany

Location

Sanofi-Aventis Investigational Site Number 276004

Mannheim, 68167, Germany

Location

Sanofi-Aventis Investigational Site Number 276002

Münster, 48149, Germany

Location

Sanofi-Aventis Investigational Site Number 276005

Recklinghausen, 45659, Germany

Location

Sanofi-Aventis Investigational Site Number 380005

Bari, 70126, Italy

Location

Sanofi-Aventis Investigational Site Number 380001

Florence, 50141, Italy

Location

Sanofi-Aventis Investigational Site Number 380002

Milan, 20121, Italy

Location

Sanofi-Aventis Investigational Site Number 380003

Taormina, 98039, Italy

Location

Sanofi-Aventis Investigational Site Number 380004

Torino, 10126, Italy

Location

Sanofi-Aventis Investigational Site Number 643002

Pyatigorsk, 357500, Russia

Location

Sanofi-Aventis Investigational Site Number 643005

Saint Petersburg, 197758, Russia

Location

Sanofi-Aventis Investigational Site Number 643001

Sochi, 354057, Russia

Location

Sanofi-Aventis Investigational Site Number 410003

Busan, 614-735, South Korea

Location

Sanofi-Aventis Investigational Site Number 410004

Cheongju-si, 361-711, South Korea

Location

Sanofi-Aventis Investigational Site Number 410005

Daegu, 700-721, South Korea

Location

Sanofi-Aventis Investigational Site Number 410002

Daejeon, South Korea

Location

Sanofi-Aventis Investigational Site Number 410007

Goyang-Si, Gyeonggi-Do, 410-769, South Korea

Location

Sanofi-Aventis Investigational Site Number 410006

Seoul, 120-752, South Korea

Location

Sanofi-Aventis Investigational Site Number 410001

Seoul, 152-703, South Korea

Location

Sanofi-Aventis Investigational Site Number 410008

Ulsan, 682-714, South Korea

Location

Sanofi-Aventis Investigational Site Number 724005

Barcelona, 08036, Spain

Location

Sanofi-Aventis Investigational Site Number 724004

Madrid, 28007, Spain

Location

Sanofi-Aventis Investigational Site Number 724001

Madrid, 28040, Spain

Location

Sanofi-Aventis Investigational Site Number 724002

Sabadell, 08208, Spain

Location

Sanofi-Aventis Investigational Site Number 724007

Santiago de Compostela, 15706, Spain

Location

Sanofi-Aventis Investigational Site Number 724003

Valencia, 46009, Spain

Location

Sanofi-Aventis Investigational Site Number 826004

Leeds, LS9 7TF, United Kingdom

Location

Sanofi-Aventis Investigational Site Number 826001

Leicester, LE1 5WW, United Kingdom

Location

Sanofi-Aventis Investigational Site Number 826002

Manchester, M20 4BX, United Kingdom

Location

Sanofi-Aventis Investigational Site Number 826003

Slough, SL2 4HL, United Kingdom

Location

Sanofi-Aventis Investigational Site Number 826005

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27091810 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

aflibercept; Oxaliplatin; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Limitations and Caveats

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.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-Us@sanofi.com

Study Officials

• John Zalcberg, MD

  Peter Mc Callum Cancer Centre, Melbourne, Australia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2009
• First Posted: February 25, 2009
• Study Start: February 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: January 1, 2012
• Last Updated: June 7, 2016
• Results First Posted: June 25, 2013

Record last verified: 2016-05

Locations

AU (3); IT (5); RU (3); KR (8); ES (6); GB (5); DE (7)