A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.

NCT00778102 | Completed Phase 2 Results

• 2 other identifiers: MO187252007-007863-26
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 19

Brief Summary

This 2 arm study will compare the resection rate of liver metastases and safety of surgery in patients with metastatic colorectal cancer and primarily unresectable liver metastases receiving treatment with Avastin in combination with 5-FU, leucovorin and oxaliplatin with irinotecan (FOLFOXIRI) or without irinotecan (mFOLFOX-6) as first line treatment. Patients will be randomized to receive Avastin (5mg/kg iv every 2 weeks) in combination with each of these two standard neoadjuvant chemotherapy regimens. The anticipated time on study treatment is until surgery, disease progression, unacceptable toxicity or patient refusal, and the target sample size is \<100 individuals.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor

  Following resective surgery, participants were evaluated for complete resection (R0) or the presence of microscopic (R1) or macroscopic (R2) residual tumor. The percentage of participants within each residual tumor classification was calculated as \[number of participants with R0, R1, and/or R2 divided by the total number of participants\] multiplied by 100. Associated 95% confidence intervals were calculated for one-sample binomial using the Clopper-Pearson method.

  Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

Secondary Outcomes (13)

• Time to Resection

  Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)

• Percentage of Participants With Histopathological Response

  Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

• Percentage of Participants With Complete or Major Histopathological Response

  Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)

• Percentage of Participants Experiencing Relapse Following Curative Resection

  Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

• Relapse-Free Survival (RFS)

  Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)

Study Arms (2)

1

EXPERIMENTAL

Drug: 5-FU; Drug: Leucovorin; Drug: Oxaliplatin; Drug: bevacizumab [Avastin]

2

ACTIVE COMPARATOR

Drug: 5-FU; Drug: Irinotecan; Drug: Leucovorin; Drug: Oxaliplatin; Drug: bevacizumab [Avastin]

Interventions

5-FU DRUG

Bolus 400mg/m2, day 1 every 2 weeks

1

Irinotecan DRUG

165mg/m2 1-hour iv infusion, day 1 every 2 weeks

2

Leucovorin DRUG

400mg/m2 2-hour iv infusion, day 1 every 2 weeks

1

Oxaliplatin DRUG

85mg/m2 2-hour iv infusion, day 1 every 2 weeks

1; 2

bevacizumab [Avastin] DRUG

5mg/kg iv day 1 every 2 weeks

1; 2

Eligibility Criteria

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

You may qualify if:

• adult patients, \>=18 years of age;
• unresectable liver metastasis secondary to cancer of colon or rectum;
• scheduled for standard first line chemotherapy;
• ECOG performance score of 0 or 1;
• condition feasible for major abdominal surgery after first line treatment.

You may not qualify if:

• diagnosis of metastatic disease \>3 months prior to study entry;
• evidence of extrahepatic disease, diffuse peritoneal carcinosis or involvement of celiac lymph nodes;
• prior systemic or local treatment of metastatic disease;
• prior (neo)adjuvant chemotherapy/radiotherapy completed within 6 months prior to study entry;
• history or evidence of CNS disease unrelated to cancer.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (19)

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

Bordeaux, 33075, France

Location

Unknown Facility

Créteil, 94010, France

Location

Unknown Facility

Le Mans, 72037, France

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Lyon, 69373, France

Location

Unknown Facility

Montpellier, 34298, France

Location

Unknown Facility

Villejuif, 94804, France

Location

Unknown Facility

Palma de Mallorca, Balearic Islands, 07198, Spain

Location

Unknown Facility

Girona, Girona, 17007, Spain

Location

Unknown Facility

Donostia / San Sebastian, Guipuzcoa, 20080, Spain

Location

Unknown Facility

Santiago de Compostela, La Coruña, 15706, Spain

Location

Unknown Facility

Madrid, Madrid, 28007, Spain

Location

Unknown Facility

Madrid, Madrid, 28046, Spain

Location

Unknown Facility

Valencia, Valencia, 46026, Spain

Location

Unknown Facility

London, WC1E 6DD, United Kingdom

Location

Unknown Facility

Manchester, M20 4QL, United Kingdom

Location

Unknown Facility

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Unknown Facility

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.

  PMID: 32816630 DERIVED

• Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P, Rivoire M, Mudan S, Lasserre S, Hermann F, Waterkamp D, Adam R. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23.

  PMID: 25538173 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin; Bevacizumab

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

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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: October 22, 2008
• First Posted: October 23, 2008
• Study Start: October 1, 2008
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 2, 2016
• Results First Posted: August 7, 2015

Record last verified: 2016-11

Locations

AU (1); GB (4); ES (7); FR (7)