Second Line ColoRectal Cancer Therapy in Combination With Combination of FOL- Folinic Acid(Leucovorin), F - Fluorouracil and OX - Oxaliplatin (FOLFOX) (HORIZON I)

A Study to Compare the Efficacy of AZD2171 in Combination With 5-fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX) and the Efficacy of Bevacizumab in Combination With FOLFOX in the Second-line Treatment of Patients With Metastatic Colorectal Cancer

The primary purpose of this study is to compare the efficacy of AZD2171 in combination with FOLFOX to the efficacy of bevacizumab in combination with FOLFOX, in the second-line treatment of patients with metastatic colorectal cancer

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: Bevacizumab; Drug: AZD2171; Drug: 5-fluorouracil; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Research Site
  • Wels, Austria
    • Research Site
  • Wien, Austria
    • Research Site
• Belgium
  • Bonheiden, Belgium
    • Research Site
  • Brussels, Belgium
    • Ressearch Site
  • Edegem, Belgium
    • Research Site
  • Gent, Belgium
    • Research Site
  • Leuven, Belgium
    • Research Site
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Research Site
  • New Brunswick
    • Moncton, New Brunswick, Canada
      • Research Site
  • Ontario
    • Kingston, Ontario, Canada
      • Research Site
    • Ottawa, Ontario, Canada
      • Research Site
    • Sudbury, Ontario, Canada
      • Research Site
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada
      • Research Site
• Czech Republic
  • Chomutov, Czech Republic
    • Research Site
  • Nova Ves Pod Plesi, Czech Republic
    • Research Site
  • Pardubice, Czech Republic
    • Research Site
  • Praha, Czech Republic
    • Research Site
• France
  • Montpellier, France
    • Research Site
  • Saint Herblain, France
    • Research Site
• Germany
  • Berlin, Germany
    • Research Site
  • Freiburg, Germany
    • Research Site
  • Halle, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Heidelberg, Germany
    • Research Site
  • München, Germany
    • Research Site
  • Stuttgart, Germany
    • Research Site
• Italy
  • Genova, Italy
    • Research Site
  • La Torretta, Italy
    • Research Site
  • Milano, Italy
    • Research Site
  • Napoli, Italy
    • Research Site
  • Rozzano, Italy
    • Research Site
• Spain
  • A Coruña, Spain
    • Research Site
  • Barcelona, Spain
    • Research Site
  • Madrid, Spain
    • Research Site
  • Valencia, Spain
    • Research Site
  • Zaragoza, Spain
    • Research Site
• United Kingdom
  • Glasgow, United Kingdom
    • Research Site
  • Ipswich, United Kingdom
    • Research Site
  • Maidstone, United Kingdom
    • Research Site
  • Newcastle-upon-tyne, United Kingdom
    • Research Site
  • Sutton, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of colon or rectal cancer,
• Received prior systemic therapy for cancer,
• Cancer must have progressed during or after first treatment

Exclusion Criteria:

• Prior treatment with a VEGF inhibitor,
• Poorly controlled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Bevacizumab + FOLFOX	Drug: Leucovorin; intravenous infusion; Drug: Bevacizumab; intravenous infusion; Other Names: Avastin®; Drug: 5-fluorouracil; intravenous infusion; Other Names: 5-FU; Drug: Oxaliplatin; intravenous infusion; Other Names: Eloxatin®
Experimental: 2; AZD2171 + FOLFOX	Drug: Leucovorin; intravenous infusion; Drug: AZD2171; oral tablet; Other Names: RECENTIN™; cediranib; Drug: 5-fluorouracil; intravenous infusion; Other Names: 5-FU; Drug: Oxaliplatin; intravenous infusion; Other Names: Eloxatin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Number of months from randomisation to the earlier date of objective progression or death	Randomisation to data cut-off date of November 2007

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Per RECIST Criteria (V1.0) and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >= ##% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Confirmed Partial Response (PR) or Complete Response (CR) as defined by RECIST.	Randomisation to data cut-off date of November 2007
Overall Survival	Number of months from randomisation to the date of death from any cause	Randomisation to data cut-off date of 30 January 2009
Quality Of Live(QOL) : Time to Worsening of Tissue Oxygen Index (TOI)	Time when a sustained clinically important deterioration in TOI has been recorded: derived from the FACT-C questionnaires	Randomisation to data cut-off date of November 2007
QOL: Time to Worsening of Treatment-free Survival (TFS)	Time when a sustained clinically important deterioration in TFS has been recorded: derived from the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaires	Randomisation to data cut-off date of November 2007
QOL: Time to Worsening of Clear Cell Sarcoma (CCS)	Time when a sustained clinically important deterioration in CCS has been recorded: derived from the FACT-C questionnaires	Randomisation to data cut-off date of November 2007
QOL: Time to Worsening of FACT Colorectal Cancer Symptom Index(FCSI)	Time when a sustained clinically important deterioration in CCS has been recorded: derived from the FACT-C questionnaires	Randomisation to data cut-off date of November 2007

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: January 17, 2006
• First Submitted That Met QC Criteria: January 17, 2006
• First Posted (Estimate): January 19, 2006

Study Record Updates

• Last Update Posted (Estimate): October 24, 2012
• Last Update Submitted That Met QC Criteria: September 24, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: metastatic colorectal cancer; Colorectal Cancer; phase II; RECENTIN; AZD2171
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Protein Kinase Inhibitors; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Cediranib
• Other Study ID Numbers: D8480C00041; EUDRACT number 2005-003443-31; HORIZON I