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NCT00384176: HORIZON III

First Line Metastatic Colorectal Cancer Therapy in Combination With FOLFOX

Completed Phase 2, PHASE3 Results posted Last updated 14 April 2017
What this trial tests

Phase 2, PHASE3 trial testing Cediranib in Colorectal Cancer in 1,814 participants. Completed in 19 August 2015.

Timeline
30 August 2006
Primary endpoint
15 November 2009
19 August 2015

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment1,814
Start date30 August 2006
Primary completion15 November 2009
Estimated completion19 August 2015
Sites280 locations across Italy, Finland, Taiwan, Vietnam, Poland, Philippines, Russia, Turkey (Türkiye)

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival Primary · Baseline then at Weeks 8, 16, 24 and then every 12 weeks until progression

Progression is defined as the number of months from randomisation until progressive disease based on RECIST (progression of target lesions, clear progression of existing non-target lesions or the appearance of one or more new lesions) or death in the absence of progression.

GroupValue95% CI
Cediranib 20 mg9.96.3 – 13.5
Bevacizumab 5 mg/kg10.36.5 – 14.1
Overall Survival Secondary · Randomisation until data cut-off

Number of months from randomisation to the date of death from any cause

GroupValue95% CI
Cediranib 20 mg22.813.3 – 32.3
Bevacizumab 5 mg/kg21.312.2 – 32.8
Objective Response Rate Secondary · Up until data cut-off

Objective response rate is Complete Response (CR) + Partial Response (PR) as defined below: CR = Disappearance of all target lesions. PR = At least a 30% decrease in the sum of longest diameters (LDs) of target lesions, taking as reference the baseline sum of LDs.

GroupValue95% CI
Cediranib 20 mg328
Bevacizumab 5 mg/kg337
Duration of Response Secondary · Up until data cut-off date of 15/11/2007

Duration of Response is calculated as the time from the first recording of CR/PR until the patient progresses, regardless of whether the patient was still taking study medication. Only confirmed responses are included in the calculation. For patients who had not progressed, the end date used in the calculation of duration of response is the data cut-off date of 15th November 2009.

GroupValue95% CI
Cediranib 20 mg8.66.1 – 12.1
Bevacizumab 5 mg/kg9.66.5 – 13.6
Percentage Change in Tumour Size Secondary · Baseline to Week 8

Percentage change in tumour size from baseline to first RECIST assessment (Week 8) ((Week 8 - baseline)/baseline)\*100

GroupValue95% CI
Cediranib 20 mg-23.2± 21.8
Bevacizumab 5 mg/kg-22.1± 19.55
Time to Worsening of Health Related Quality of Life (QOL) Based on the FACT Colorectal Symptom Index (FCSI) Secondary · Baseline through to data cut-off

Time to worsening of symptoms, as measured by the FACT colorectal symptom index (FCSI), will be defined as the time when a sustained clinically important deterioration in the total score from the FCSI has been recorded.

GroupValue95% CI
Cediranib 20 mg17056 – 328
Bevacizumab 5 mg/kg245112 – 348

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cediranib 20 mg
Serious: 275/705 (39%)
Deaths:
Cediranib 30 mg
Serious: 90/191 (47%)
Deaths:
1Bevacizumab 5mg/kg
Serious: 231/704 (33%)
Deaths:

Serious adverse events (308 terms)

ReactionSystemCediranib 20 mgCediranib 30 mg1Bevacizumab 5mg/kg
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
Intestinal ObstructionGastrointestinal disorders
VomitingGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal PainGastrointestinal disorders
NauseaGastrointestinal disorders
PneumoniaInfections and infestations
Deep Vein ThrombosisVascular disorders
HypertensionVascular disorders
DehydrationMetabolism and nutrition disorders
IleusGastrointestinal disorders
Small Intestinal ObstructionGastrointestinal disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
Intestinal PerforationGastrointestinal disorders
Catheter Related InfectionInfections and infestations
SepsisInfections and infestations
Urinary Tract InfectionInfections and infestations
Rectal HaemorrhageGastrointestinal disorders
Drug HypersensitivityImmune system disorders
Anal FistulaGastrointestinal disorders
Other adverse events (52 terms — click to expand)

ReactionSystemCediranib 20 mgCediranib 30 mg1Bevacizumab 5mg/kg
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
NeutropeniaBlood and lymphatic system disorders
HypertensionVascular disorders
StomatitisGastrointestinal disorders
VomitingGastrointestinal disorders
Neuropathy PeripheralNervous system disorders
ConstipationGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Decreased AppetiteMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal PainGastrointestinal disorders
ParaesthesiaNervous system disorders
Peripheral Sensory NeuropathyNervous system disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
HeadacheNervous system disorders
Palmar-Plantar Erythrodysaesthesia SyndromeSkin and subcutaneous tissue disorders
AstheniaGeneral disorders
DysgeusiaNervous system disorders
Abdominal Pain UpperGastrointestinal disorders
Weight DecreasedInvestigations
AnaemiaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Back PainMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypokalaemiaMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
DyspepsiaGastrointestinal disorders
InsomniaPsychiatric disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
Drug HypersensitivityImmune system disorders
NasopharyngitisInfections and infestations
ProteinuriaRenal and urinary disorders
Pain In ExtremityMusculoskeletal and connective tissue disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
Urinary Tract InfectionInfections and infestations

Most-reported serious reactions: Diarrhoea, Pyrexia, Pulmonary Embolism, Febrile Neutropenia, Intestinal Obstruction, Vomiting, Neutropenia, Abdominal Pain.

Data from ClinicalTrials.gov NCT00384176 adverse events section.

Sponsor's own description

The purpose of this study is to see if Cediranib in combination with FOLFOX is effective in treating metastatic colorectal cancer and to see how it compares with Avastin (Bevacizumab) in combination with FOLFOX.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  2. Anti-VEGF therapies in the clinic.
    Meadows KL, Hurwitz HI. · · 2012 · cited 165× · PMID 23028128 · DOI 10.1101/cshperspect.a006577
  3. Therapeutic advances of targeting receptor tyrosine kinases in cancer.
    Tomuleasa C, Tigu AB, Munteanu R, Moldovan CS, et al · · 2024 · cited 133× · PMID 39138146 · DOI 10.1038/s41392-024-01899-w
  4. Small molecule inhibitors targeting the cancers.
    Liu GH, Chen T, Zhang X, Ma XL, et al · · 2022 · cited 127× · PMID 36254250 · DOI 10.1002/mco2.181
  5. Angiogenesis in metastatic colorectal cancer and the benefits of targeted therapy.
    Sun W. · · 2012 · cited 91× · PMID 23057939 · DOI 10.1186/1756-8722-5-63
  6. The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer.
    Chen Y, Zheng X, Wu C. · · 2021 · cited 77× · PMID 34925375 · DOI 10.3389/fimmu.2021.792691
  7. Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy.
    Jürgensmeier JM, Schmoll HJ, Robertson JD, Brooks L, et al · · 2013 · cited 55× · PMID 23449351 · DOI 10.1038/bjc.2013.79
  8. Anti-VEGF agents in metastatic colorectal cancer (mCRC): are they all alike?
    Saif MW. · · 2013 · cited 35× · PMID 23807861 · DOI 10.2147/cmar.s45193

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00384176.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing