Back to resultsCediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer (HORIZON II)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cediranib
FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)
XELOX (Capecitabine and Oxaliplatin)
Cediranib Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Colorectal Cancer, Cediranib, RECENTIN
Eligibility Criteria
Inclusion Criteria:
- Written Informed Consent
- Carcinoma of the colon or rectum
- One or more measurable lesions
Exclusion Criteria:
- Adjuvant/neoadjuvant therapy within 6-12 months of study entry
- Untreated unstable brain or meningeal metastases
- Specific laboratory ranges
- Specific cardiovascular problems
- Participation in other trials within 30 days
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Placebo Comparator
Experimental
Experimental
Arm Label
FOLFOX + placebo Cediranib
Xelox + placebo Cediranib
FOLFOX + Cediranib
XELOX + Cediranib
Arm Description
FOLFOX + placebo Cediranib
Xelox + placebo Cediranib
FOLFOX + Cediranib
XELOX + Cediranib
Outcomes
Primary Outcome Measures
Progression-free Survival
RECIST criteria defined as follows: Target lesions Complete Response (CR) Disappearance of all target lesions Partial Response (PR) At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non-target lesions Complete Response (CR) Disappearance of all non-target lesions Non-Complete Response (non-CR/Non- Progression [non-PD]) Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing nontarget lesions.
Overall Survival
Number of months from randomisation to the date of death from any cause
Secondary Outcome Measures
Overall Response Rate
Objective tumour response(defined as a confirmed response of CR or PR).The definition for a confirmed response was met when an initial RECIST response of PR/CR was confirmed at the next scheduled visit as a PR/CR according to an evaluable assessment.Intervening assessments of non-evaluable or stable disease were allowable as long as the initial RECIST response was confirmed.RECIST criteria defined as follows: Target lesions Complete Response(CR)Disappearance of all target lesions Partial Response (PR).At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Non-target lesions Complete Response (CR) Disappearance of all non-target lesi
Best Percentage Change in Tumour Size
Maximum percentage reduction or minimum percentage increase in tumour size where size is the sum of the longest diameters of the target lesions
Duration of Response
Based on RECIST measurements taken throughout the study and best objective tumour response at the defined analysis cut-off point. Measured from the time the criteria for CR/PR are first met (whichever is recorded first) until the patient progresses or dies.
Rate of Resection of Liver Metastases
Number of patients undergoing liver resection, based on patients with liver disease at baseline
Time to Wound Healing Complications
Number of days from post-randomisation surgery until wound healing complications
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00399035
Brief Title
Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer
Acronym
HORIZON II
Official Title
A Randomised, Double-blind, Phase III Study to Compare the Efficacy and Safety of Cediranib (AZD2171, RECENTIN™) When Added to 5 Fluorouracil, Leucovorin and Oxaliplatin (FOLFOX) or Capecitabine and Oxaliplatin (XELOX) With the Efficacy and Safety of Placebo When Added to FOLFOX or XELOX in Patients With Previously Untreated Metastatic Colorectal Cancer.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to determine if Cediranib when added to chemotherapy is more effective than chemotherapy alone in prolonging life expectancy and slowing disease progression in patients with previously untreated metastatic colorectal cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Colorectal Cancer, Cediranib, RECENTIN
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1254 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFOX + placebo Cediranib
Arm Type
Placebo Comparator
Arm Description
FOLFOX + placebo Cediranib
Arm Title
Xelox + placebo Cediranib
Arm Type
Placebo Comparator
Arm Description
Xelox + placebo Cediranib
Arm Title
FOLFOX + Cediranib
Arm Type
Experimental
Arm Description
FOLFOX + Cediranib
Arm Title
XELOX + Cediranib
Arm Type
Experimental
Arm Description
XELOX + Cediranib
Intervention Type
Drug
Intervention Name(s)
Cediranib
Other Intervention Name(s)
AZD2171, RECENTIN™
Intervention Description
oral tablet
Intervention Type
Drug
Intervention Name(s)
FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)
Other Intervention Name(s)
Other Names:, 5-FU, Drug: Leucovorin (in FOLFOX), intravenous infusion, Drug: Oxaliplatin (in FOLFOX), Eloxatin®
Intervention Description
intravenous infusion
Intervention Type
Drug
Intervention Name(s)
XELOX (Capecitabine and Oxaliplatin)
Other Intervention Name(s)
Xeloda® + Eloxatin®
Intervention Description
intravenous oxaliplatin 130 mg/ m^2(day 1) followed by oral capecitabine 1,000 mg/ m^2twice daily (day 1 to day 15)
Intervention Type
Drug
Intervention Name(s)
Cediranib Placebo
Intervention Description
oral tablet
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
RECIST criteria defined as follows: Target lesions Complete Response (CR) Disappearance of all target lesions Partial Response (PR) At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD.Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non-target lesions Complete Response (CR) Disappearance of all non-target lesions Non-Complete Response (non-CR/Non- Progression [non-PD]) Persistence of one or more non-target lesion or/and maintenance of tumour marker level above the normal limits. Progression (PD) Unequivocal progression of existing nontarget lesions.
Time Frame
RECIST assessed at baseline every 6 weeks through to week 24 and 12 week thereafter through to progression or data cut off date of 21/03/10 whichever was earliest.
Title
Overall Survival
Description
Number of months from randomisation to the date of death from any cause
Time Frame
Baseline through to date of death upto and including data cut off date of 21/03/10
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Objective tumour response(defined as a confirmed response of CR or PR).The definition for a confirmed response was met when an initial RECIST response of PR/CR was confirmed at the next scheduled visit as a PR/CR according to an evaluable assessment.Intervening assessments of non-evaluable or stable disease were allowable as long as the initial RECIST response was confirmed.RECIST criteria defined as follows: Target lesions Complete Response(CR)Disappearance of all target lesions Partial Response (PR).At least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) At least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded (either at baseline or at previous assessment since treatment began).Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.Non-target lesions Complete Response (CR) Disappearance of all non-target lesi
Time Frame
Baseline through to date of death upto and including data cut off date of 21/03/10
Title
Best Percentage Change in Tumour Size
Description
Maximum percentage reduction or minimum percentage increase in tumour size where size is the sum of the longest diameters of the target lesions
Time Frame
Baseline through to date of death upto and including data cut off date of 21/03/10
Title
Duration of Response
Description
Based on RECIST measurements taken throughout the study and best objective tumour response at the defined analysis cut-off point. Measured from the time the criteria for CR/PR are first met (whichever is recorded first) until the patient progresses or dies.
Time Frame
Treatment period from initial response up until data cut-off date of 21/03/10
Title
Rate of Resection of Liver Metastases
Description
Number of patients undergoing liver resection, based on patients with liver disease at baseline
Time Frame
Post-randomisation until end of study
Title
Time to Wound Healing Complications
Description
Number of days from post-randomisation surgery until wound healing complications
Time Frame
Post-randomisation until end of study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written Informed Consent
Carcinoma of the colon or rectum
One or more measurable lesions
Exclusion Criteria:
Adjuvant/neoadjuvant therapy within 6-12 months of study entry
Untreated unstable brain or meningeal metastases
Specific laboratory ranges
Specific cardiovascular problems
Participation in other trials within 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Robertson
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Buenos Aires City
Country
Argentina
Facility Name
Research Site
City
Capital Federal
Country
Argentina
Facility Name
Research Site
City
Ciudad de Buenos Aires
Country
Argentina
Facility Name
Research Site
City
Córdoba
Country
Argentina
Facility Name
Research Site
City
Resistencia
Country
Argentina
Facility Name
Research Site
City
Rosario
Country
Argentina
Facility Name
Research Site
City
Santa Fe
Country
Argentina
Facility Name
Research Site
City
Ashford
Country
Australia
Facility Name
Research Site
City
Camperdown
Country
Australia
Facility Name
Research Site
City
Heidelberg
Country
Australia
Facility Name
Research Site
City
Hornsby
Country
Australia
Facility Name
Research Site
City
Liverpool
Country
Australia
Facility Name
Research Site
City
Waratah
Country
Australia
Facility Name
Research Site
City
Wodonga
Country
Australia
Facility Name
Research Site
City
Curitiba
Country
Brazil
Facility Name
Research Site
City
Goiânia
Country
Brazil
Facility Name
Research Site
City
Jaú
Country
Brazil
Facility Name
Research Site
City
Porto Alegre
Country
Brazil
Facility Name
Research Site
City
Rio de Janeiro
Country
Brazil
Facility Name
Research Site
City
Salvador
Country
Brazil
Facility Name
Research Site
City
Santo André
Country
Brazil
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Research Site
City
Sao Paulo
Country
Brazil
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Research Site
City
São Paulo
Country
Brazil
Facility Name
Research Site
City
Plovdiv
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Stara Zagora
Country
Bulgaria
Facility Name
Research Site
City
Varna
Country
Bulgaria
Facility Name
Research Site
City
Veliko Tarnovo
Country
Bulgaria
Facility Name
Research Site
City
Vratza
Country
Bulgaria
Facility Name
Research Site
City
Beijing
Country
China
Facility Name
Research Site
City
Changchun
Country
China
Facility Name
Research Site
City
Chengdu
Country
China
Facility Name
Research Site
City
ChongQing
Country
China
Facility Name
Research Site
City
Fuzhou
Country
China
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Research Site
City
Guangzhou
Country
China
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Research Site
City
Hangzhou
Country
China
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City
Nanjing
Country
China
Facility Name
Research Site
City
Nanning
Country
China
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City
Shanghai
Country
China
Facility Name
Research Site
City
Tianjin
Country
China
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Research Site
City
Brno
Country
Czech Republic
Facility Name
Research Site
City
Ceske Budejovice
Country
Czech Republic
Facility Name
Research Site
City
Cheb
Country
Czech Republic
Facility Name
Research Site
City
Jicin
Country
Czech Republic
Facility Name
Research Site
City
Jihlava
Country
Czech Republic
Facility Name
Research Site
City
Olomouc
Country
Czech Republic
Facility Name
Research Site
City
Ostrava
Country
Czech Republic
Facility Name
Research Site
City
Praha 6
Country
Czech Republic
Facility Name
Research Site
City
Pribram - Zdabor
Country
Czech Republic
Facility Name
Research Site
City
Sumperk
Country
Czech Republic
Facility Name
Research Site
City
Zlin
Country
Czech Republic
Facility Name
Research Site
City
Znojmo
Country
Czech Republic
Facility Name
Research Site
City
Essen
Country
Germany
Facility Name
Research Site
City
Freiburg
Country
Germany
Facility Name
Research Site
City
Goslar
Country
Germany
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Hildesheim
Country
Germany
Facility Name
Research Site
City
Mannheim
Country
Germany
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Debrecen
Country
Hungary
Facility Name
Research Site
City
Györ
Country
Hungary
Facility Name
Research Site
City
Kecskemét
Country
Hungary
Facility Name
Research Site
City
Nyíregyháza
Country
Hungary
Facility Name
Research Site
City
Szombathely
Country
Hungary
Facility Name
Research Site
City
Zalaegerszeg
Country
Hungary
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Research Site
City
Hyderabad
Country
India
Facility Name
Research Site
City
Trivandrum
Country
India
Facility Name
Research Site
City
Goyang-si
Country
Korea, Republic of
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Research Site
City
Seoul
Country
Korea, Republic of
Facility Name
Research Site
City
Cebu City
Country
Philippines
Facility Name
Research Site
City
Davao City
Country
Philippines
Facility Name
Research Site
City
Iloilo
Country
Philippines
Facility Name
Research Site
City
Quezon City
Country
Philippines
Facility Name
Research Site
City
Quezon
Country
Philippines
Facility Name
Research Site
City
Bydgoszcz
Country
Poland
Facility Name
Research Site
City
Gdańsk
Country
Poland
Facility Name
Research Site
City
Gliwice
Country
Poland
Facility Name
Research Site
City
Kraków
Country
Poland
Facility Name
Research Site
City
Olsztyn
Country
Poland
Facility Name
Research Site
City
Toruń
Country
Poland
Facility Name
Research Site
City
Wrocław
Country
Poland
Facility Name
Research Site
City
Bellinzona
Country
Switzerland
Facility Name
Research Site
City
Lausanne
Country
Switzerland
Facility Name
Research Site
City
Locarno
Country
Switzerland
Facility Name
Research Site
City
Zürich
Country
Switzerland
Facility Name
Research Site
City
Tainan
Country
Taiwan
Facility Name
Research Site
City
Taipei
Country
Taiwan
Facility Name
Research Site
City
Aberdeen
Country
United Kingdom
Facility Name
Research Site
City
Belfast
Country
United Kingdom
Facility Name
Research Site
City
Leicester
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23510802
Citation
Smith JC, Brooks L, Hoff PM, McWalter G, Dearden S, Morgan SR, Wilson D, Robertson JD, Jurgensmeier JM. KRAS mutations are associated with inferior clinical outcome in patients with metastatic colorectal cancer, but are not predictive for benefit with cediranib. Eur J Cancer. 2013 Jul;49(10):2424-32. doi: 10.1016/j.ejca.2013.02.023. Epub 2013 Mar 16.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=424&filename=CSR-D8480C00051.pdf
Description
CSR-D8480C00051.pdf
Learn more about this trial
Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer
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