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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: June 18, 2015
Last verified: June 2015
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 = 1814 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.

200 patients dropped prior to treatment. Study was set up as a phase II/III study. Participants were enrolled into both phases if they participated in both Phase II/III, but are only counted once in the Enrollment Number and in the Results.


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.
No text entered.

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 
Overall Participants Analyzed 
[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) 
[1] Age at informed consent
Gender [1] 
[Units: Participants]
       
Female   297   299   73   669 
Male   412   414   119   945 
[1] Gender at informed consent


  Outcome Measures
  Show All Outcome Measures

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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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: June 18, 2015
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
United States: Food and Drug Administration