Metastatic Colorectal CancerPhase 3HORIZON IINCT00399035
Cediranib (AZD2171, RECENTIN™) in Addition to Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer
A Phase 3 study testing Cediranib, FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) and XELOX (Capecitabine and Oxaliplatin) in people with Metastatic Colorectal Cancer, run by AstraZeneca at 90 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Cediranib, FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) and XELOX (Capecitabine and Oxaliplatin)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,254 participants
- Where
- 90 sitesin 15 countries
- Study dates
- Nov 2006to Aug 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written Informed Consent
- Carcinoma of the colon or rectum
- One or more measurable lesions
Who cannot join
- 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
Trial locations and contacts
90 sites in 15 countries.
90 sites in 15 countries
Czechia12 sites
Research Site
Brno
Research Site
České Budějovice
Research Site
Cheb
Research Site
Jičín
Research Site
Jihlava
Research Site
Olomouc
Research Site
Ostrava
Research Site
Prague
Research Site
Pribram - Zdabor
Research Site
Šumperk
Research Site
Zlín
Research Site
Znojmo
China11 sites
Research Site
Beijing
Research Site
Changchun
Research Site
Chengdu
Research Site
Chongqing
Research Site
Fuzhou
Research Site
Guangzhou
Research Site
Hangzhou
Research Site
Nanjing
Research Site
Nanning
Research Site
Shanghai
Research Site
Tianjin
Brazil8 sites
Research Site
Curitiba
Research Site
Goiânia
Research Site
Jaú
Research Site
Porto Alegre
Research Site
Rio de Janeiro
Research Site
Salvador
Research Site
Santo André
Research Site
São Paulo
Argentina7 sites
Research Site
Buenos Aires
Research Site
Capital Federal
Research Site
Ciudad de Buenos Aires
Research Site
Córdoba
Research Site
Resistencia
Research Site
Rosario
Research Site
Santa Fe
Australia7 sites
Research Site
Ashford
Research Site
Camperdown
Research Site
Heidelberg
Research Site
Hornsby
Research Site
Liverpool
Research Site
Waratah
Research Site
Wodonga
Hungary7 sites
Research Site
Budapest
Research Site
Debrecen
Research Site
Győr
Research Site
Kecskemét
Research Site
Nyíregyháza
Research Site
Szombathely
Research Site
Zalaegerszeg
Poland7 sites
Research Site
Bydgoszcz
Research Site
Gdansk
Research Site
Gliwice
Research Site
Krakow
Research Site
Olsztyn
Research Site
Torun
Research Site
Wroclaw
Bulgaria6 sites
Research Site
Plovdiv
Research Site
Sofia
Research Site
Stara Zagora
Research Site
Varna
Research Site
Veliko Tarnovo
Research Site
Vratsa
Germany6 sites
Research Site
Essen
Research Site
Freiburg im Breisgau
Research Site
Goslar
Research Site
Hamburg
Research Site
Hildesheim
Research Site
Mannheim
Philippines5 sites
Research Site
Cebu City
Research Site
Davao City
Research Site
Iloilo City
Research Site
Quezon
Research Site
Quezon City
Switzerland4 sites
Research Site
Bellinzona
Research Site
Lausanne
Research Site
Locarno
Research Site
Zurich
United Kingdom4 sites
Research Site
Aberdeen
Research Site
Belfast
Research Site
Leicester
Research Site
Manchester
About this study
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.
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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Cediranib, FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), XELOX (Capecitabine and Oxaliplatin), Cediranib Placebo
- Keywords
- Colorectal Cancer, Cediranib, RECENTIN
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CediranibDrug
Also called AZD2171, RECENTIN™
oral tablet
FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)Drug
Also called Other Names:, 5-FU, Drug: Leucovorin (in FOLFOX), intravenous infusion
intravenous infusion
XELOX (Capecitabine and Oxaliplatin)Drug
Also called Xeloda® + Eloxatin®
intravenous oxaliplatin 130 mg/ m^2(day 1) followed by oral capecitabine 1,000 mg/ m^2twice daily (day 1 to day 15)
Cediranib PlaceboDrug
oral tablet
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX + placebo Cediranib | Placebo comparator | FOLFOX + placebo Cediranib Receives: Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); Drug: Cediranib Placebo |
| Xelox + placebo Cediranib | Placebo comparator | Xelox + placebo Cediranib Receives: Drug: XELOX (Capecitabine and Oxaliplatin); Drug: Cediranib Placebo |
| FOLFOX + Cediranib | Experimental | FOLFOX + Cediranib Receives: Drug: Cediranib; Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) |
| XELOX + Cediranib | Experimental | XELOX + Cediranib Receives: Drug: Cediranib; Drug: XELOX (Capecitabine and Oxaliplatin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Overall Survival
Number of months from randomisation to the date of death from any cause
Measured: Baseline through to date of death upto and including data cut off date of 21/03/10
Secondary outcomes (5)
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
Measured: Baseline through to date of death upto and including data cut off date of 21/03/10
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
Measured: Baseline through to date of death upto and including data cut off date of 21/03/10
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.
Measured: Treatment period from initial response up until data cut-off date of 21/03/10
Rate of Resection of Liver Metastases
Number of patients undergoing liver resection, based on patients with liver disease at baseline
Measured: Post-randomisation until end of study
Time to Wound Healing Complications
Number of days from post-randomisation surgery until wound healing complications
Measured: Post-randomisation until end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionMar 2010
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,254 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jane Robertson, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00399035
- Sponsor's protocol ID
- D8480C00051
- Other IDs
- EUDRACT No 2006-001194-14, HORIZON II
- Acronym
- HORIZON II
- Status last verified
- Oct 2016
- First submitted
- 13 Nov 2006
- Last updated
- 28 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 23510802
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00399035
- Acronym / sponsor ID
- HORIZON II / D8480C00051
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal Cancer, Cediranib, RECENTIN
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,254 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Mar 2010 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 14 Nov 2006 (estimated)
- Results
- Posted 30 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| FOLFOX + placebo Cediranib | Placebo comparator | Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), Drug: Cediranib PlaceboFOLFOX + placebo Cediranib |
| Xelox + placebo Cediranib | Placebo comparator | Drug: XELOX (Capecitabine and Oxaliplatin), Drug: Cediranib PlaceboXelox + placebo Cediranib |
| FOLFOX + Cediranib | Experimental | Drug: Cediranib, Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)FOLFOX + Cediranib |
| XELOX + Cediranib | Experimental | Drug: Cediranib, Drug: XELOX (Capecitabine and Oxaliplatin)XELOX + Cediranib |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written Informed Consent
- Carcinoma of the colon or rectum
- One or more measurable lesions
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CediranibAlso: AZD2171, RECENTIN™oral tablet | Drug | FOLFOX + Cediranib, XELOX + Cediranib |
| FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)Also: Other Names:, 5-FU, Drug: Leucovorin (in FOLFOX), intravenous infusionintravenous infusion | Drug | FOLFOX + Cediranib, FOLFOX + placebo Cediranib |
| XELOX (Capecitabine and Oxaliplatin)Also: Xeloda® + Eloxatin®intravenous oxaliplatin 130 mg/ m^2(day 1) followed by oral capecitabine 1,000 mg/ m^2twice daily (day 1 to day 15) | Drug | XELOX + Cediranib, Xelox + placebo Cediranib |
| Cediranib Placebooral tablet | Drug | FOLFOX + placebo Cediranib, Xelox + placebo Cediranib |
Primary outcome
Progression-free Survival
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.
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
Time frame: Baseline through to date of death upto and including data cut off date of 21/03/10
Number of months from randomisation to the date of death from any cause
5 secondary outcomes
Overall Response Rate
Time frame: Baseline through to date of death upto and including data cut off date of 21/03/10
Best Percentage Change in Tumour Size
Time frame: Baseline through to date of death upto and including data cut off date of 21/03/10
Duration of Response
Time frame: Treatment period from initial response up until data cut-off date of 21/03/10
Rate of Resection of Liver Metastases
Time frame: Post-randomisation until end of study
Time to Wound Healing Complications
Time frame: Post-randomisation until end of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23510802Smith 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.
- CSR-D8480C00051.pdfLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jane Robertson study director
AstraZeneca
90 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cediranib, FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) and XELOX (Capecitabine and Oxaliplatin) in people with Metastatic Colorectal Cancer, run by AstraZeneca at 90 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in Czechia, China, Brazil, Argentina, Australia and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00399035, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.