First Line Metastatic Colorectal Cancer Therapy in Combination With FOLFOX (HORIZON III)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00384176
First received: October 3, 2006
Last updated: September 23, 2013
Last verified: September 2013
Results First Received: March 7, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Colorectal Cancer
Interventions: Drug: Cediranib
Drug: Bevacizumab
Drug: 5-fluorouracil ( in FOLFOX)
Drug: Leucovorin (in FOLFOX)
Drug: Oxaliplatin (in FOLFOX)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrolled = 1805 though not all patient randomised. Randomised= Intent to treat (ITT): Cediranib 20mg 709, Cediranib 30mg 192 Bevacizumab 713; Safety: Cediranib 20mg 705, Cediranib 30mg 191 Bevacizumab 704

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Cediranib 30mg discontinued following Phase II, Cediranib 20mg chosen dose for comparing with Bevacizumab

Reporting Groups
  Description
Cediranib 20 mg

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Bevacizumab 5 mg/kg

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Cediranib 30 mg

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.

Participant Flow:   Overall Study
    Cediranib 20 mg     Bevacizumab 5 mg/kg     Cediranib 30 mg  
STARTED     709     713     192  
COMPLETED     397     394     60  
NOT COMPLETED     312     319     132  
Death                 239                 247                 105  
Withdrawal by Subject                 52                 48                 22  
Lost to Follow-up                 16                 18                 4  
Incorrect enrol/elig crit not fulfilled                 2                 3                 0  
Longer QTC as Visit 1                 1                 0                 0  
Toxicity of treatment                 1                 0                 0  
Did not receive study treatment                 0                 1                 1  
Physician Decision                 0                 2                 0  
Liver metastases, colon resec. planned                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Cediranib 20 mg

Cediranib 20 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Bevacizumab 5 mg/kg

Bevacizumab 5 mg/kg on Day 1 and every 2 weeks

+ FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Cediranib 30 mg

Cediranib 30 mg/day + FOLFOX

The FOLFOX regimen in this study was a modified FOLFOX6 regimen, repeated every 2 weeks:

  • Oxaliplatin 85 mg/m2 with leucovorin 400 mg/m2 (or equivalent folinic acid preparation) administered intravenously over 2 hours on Day 1
  • 5-FU 400 mg/m2 bolus immediately after completion of the oxaliplatin infusion on Day 1, followed immediately by 5-FU 2400 mg/m2 administered by a continuous iv infusion over 46 hours.
Total Total of all reporting groups

Baseline Measures
    Cediranib 20 mg     Bevacizumab 5 mg/kg     Cediranib 30 mg     Total  
Number of Participants  
[units: participants]
  709     713     192     1614  
Age [1]
[units: years]
Mean ± Standard Deviation
  58.1  ± 11.37     59.0  ± 10.82     59.2  ± 10.59     58.6  ± 11.1  
Gender [2]
[units: participants]
       
Female     297     299     73     669  
Male     412     414     119     945  
[1] Age at informed consent
[2] Gender at informed consent



  Outcome Measures
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1.  Primary:   Progression Free Survival   [ Time Frame: Baseline then at Weeks 8, 16, 24 and then every 12 weeks until progression ]

2.  Secondary:   Overall Survival   [ Time Frame: Randomisation until data cut-off ]

3.  Secondary:   Objective Response Rate   [ Time Frame: Up until data cut-off ]

4.  Secondary:   Duration of Response   [ Time Frame: Up until data cut-off date of 15/11/2007 ]

5.  Secondary:   Percentage Change in Tumour Size   [ Time Frame: Baseline to Week 8 ]

6.  Secondary:   Time to Worsening of Health Related Quality of Life (QOL) Based on the FACT Colorectal Symptom Index (FCSI)   [ Time Frame: Baseline through to data cut-off ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: ClinicalTrialTransparency@astrazeneca.com


No publications provided by AstraZeneca

Publications automatically indexed to this study:

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00384176     History of Changes
Other Study ID Numbers: D8480C00013, Eudract Number 2005-003440-66
Study First Received: October 3, 2006
Results First Received: March 7, 2012
Last Updated: September 23, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Austria: Federal Ministry for Health and Women
Czech Republic: State Institute for Drug Control
Belgium: Ministry of Social Affairs, Public Health and the Environment