Study With AG-013736 Combined With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00460603
First received: April 13, 2007
Last updated: November 7, 2013
Last verified: November 2013
Results First Received: March 28, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Colorectal Neoplasms
Interventions: Drug: bevacizumab
Drug: AG-013726
Drug: AG-013736 (axitinib)

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1) Bevacizumab 1 milligram per kilogram (mg/kg) intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 milligram per square meter (mg/m^2) intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-fluorouracil (5-FU) 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2) Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3) Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 4) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to irinotecan infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFOX (Cohort 5) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 6) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFOX (Cohort 7) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 8) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 7 mg to 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 9) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Axitinib + FOLFOX FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Bevacizumab + FOLFOX Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Axitinib + Bevacizumab + FOLFOX Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.

Participant Flow for 2 periods

Period 1:   Phase 1
    Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3)     Phase 1: Axitinib + FOLFIRI (Cohort 4)     Phase 1: Axitinib + FOLFOX (Cohort 5)     Phase 1: Axitinib + FOLFIRI (Cohort 6)     Phase 1: Axitinib + FOLFOX (Cohort 7)     Phase 1: Axitinib + FOLFIRI (Cohort 8)     Phase 1: Axitinib + FOLFIRI (Cohort 9)     Phase 2: Axitinib + FOLFOX     Phase 2: Bevacizumab + FOLFOX     Phase 2: Axitinib + Bevacizumab + FOLFOX  
STARTED     6     6     4     8     6     4     6     3     18     0     0     0  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     6     6     4     8     6     4     6     3     18     0     0     0  
Death                 1                 0                 0                 2                 0                 0                 0                 0                 1                 0                 0                 0  
Adverse Event                 3                 1                 1                 2                 0                 0                 3                 0                 4                 0                 0                 0  
Lack of Efficacy                 1                 0                 1                 2                 2                 2                 2                 2                 11                 0                 0                 0  
Withdrawal by Subject                 1                 2                 1                 1                 3                 0                 1                 0                 2                 0                 0                 0  
Unspecified                 0                 3                 1                 1                 1                 2                 0                 1                 0                 0                 0                 0  

Period 2:   Phase 2
    Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3)     Phase 1: Axitinib + FOLFIRI (Cohort 4)     Phase 1: Axitinib + FOLFOX (Cohort 5)     Phase 1: Axitinib + FOLFIRI (Cohort 6)     Phase 1: Axitinib + FOLFOX (Cohort 7)     Phase 1: Axitinib + FOLFIRI (Cohort 8)     Phase 1: Axitinib + FOLFIRI (Cohort 9)     Phase 2: Axitinib + FOLFOX     Phase 2: Bevacizumab + FOLFOX     Phase 2: Axitinib + Bevacizumab + FOLFOX  
STARTED     0     0     0     0     0     0     0     0     0     42     43     41  
Treated     0     0     0     0     0     0     0     0     0     39     43     41  
COMPLETED     0     0     0     0     0     0     0     0     0     0     0     0  
NOT COMPLETED     0     0     0     0     0     0     0     0     0     42     43     41  
Ongoing in study A4061008 (NCT00828919)                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Adverse Event                 0                 0                 0                 0                 0                 0                 0                 0                 0                 12                 9                 10  
Death                 0                 0                 0                 0                 0                 0                 0                 0                 0                 4                 2                 2  
Protocol Violation                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1                 0  
Lost to Follow-up                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Unspecified                 0                 0                 0                 0                 0                 0                 0                 0                 0                 6                 16                 7  
Objective Progression or Relapse                 0                 0                 0                 0                 0                 0                 0                 0                 0                 9                 10                 17  
Global Deterioration of Health Status                 0                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 0                 0                 5                 4                 5  
Randomized, but not treated                 0                 0                 0                 0                 0                 0                 0                 0                 0                 3                 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
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1) Bevacizumab 1 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2) Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3) Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 4) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to irinotecan infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFOX (Cohort 5) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 in Cycle 1 and starting from Day 1 in all subsequent cycles administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 6) FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFOX (Cohort 7) FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily starting from Day 3 to Day 12 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 8) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 7 mg to 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 1: Axitinib + FOLFIRI (Cohort 9) Axitinib (AG-13736) tablet 7 mg orally twice daily for 7 days in 2-week lead-in period prior to Day 1 Cycle 1. FOLFIRI combination chemotherapy on Day 1 of each 14-day cycle consisting of irinotecan 180 mg/m^2 intravenous infusion over 90 minutes, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with irinotecan, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 10 mg orally twice daily from Day 3 to Day 9 in each 14-day cycle administered following completion of 5-FU infusion on Day 3. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Axitinib + FOLFOX FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered prior to oxaliplatin infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Bevacizumab + FOLFOX Bevacizumab 5 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Phase 2: Axitinib + Bevacizumab + FOLFOX Bevacizumab 2 mg/kg intravenous infusion over 90 minutes on Day 1 of each 14-day cycle followed by FOLFOX combination chemotherapy on Day 1 of each 14-day cycle consisting of oxaliplatin 85 mg/m^2 intravenous infusion over 2 hours, leucovorin 400 mg/m^2 intravenous infusion over 2 hours administered concurrently with oxaliplatin, then 5-FU 400 mg/m^2 intravenous bolus injection and a subsequent 5-FU 2400 mg/m^2 intravenous infusion over 46 to 48 hours. Axitinib (AG-013736) tablet 5 mg orally twice daily in each 14-day cycle administered following bevacizumab infusion on Day 1. Dose adjustment for any drug in the combination was done for individual participants who experienced drug-related toxicity, as per investigator's discretion.
Total Total of all reporting groups

Baseline Measures
    Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 1)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 2)     Phase 1: Axitinib + Bevacizumab + FOLFOX (Cohort 3)     Phase 1: Axitinib + FOLFIRI (Cohort 4)     Phase 1: Axitinib + FOLFOX (Cohort 5)     Phase 1: Axitinib + FOLFIRI (Cohort 6)     Phase 1: Axitinib + FOLFOX (Cohort 7)     Phase 1: Axitinib + FOLFIRI (Cohort 8)     Phase 1: Axitinib + FOLFIRI (Cohort 9)     Phase 2: Axitinib + FOLFOX     Phase 2: Bevacizumab + FOLFOX     Phase 2: Axitinib + Bevacizumab + FOLFOX     Total  
Number of Participants  
[units: participants]
  6     6     4     8     6     4     6     3     18     42     43     41     187  
Age, Customized  
[units: Participants]
                         
Less than (<) 18 years     0     0     0     0     0     0     0     0     0     0     0     0     0  
18 to 44 years     1     2     0     1     1     1     0     0     1     2     4     8     21  
45 to 64 years     2     1     3     3     2     1     5     3     13     22     18     23     96  
Greater than or equal to (>=) 65 years     3     3     1     4     3     2     1     0     4     18     21     10     70  
Gender  
[units: Participants]
                         
Female     3     1     2     2     1     2     2     0     7     17     15     15     67  
Male     3     5     2     6     5     2     4     3     11     25     28     26     120  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Objective Response: Phase 2   [ Time Frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) ]

2.  Secondary:   Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6 and 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

3.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

4.  Secondary:   Maximum Observed Plasma Concentration (Cmax) For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

5.  Secondary:   Minimum Observed Plasma Trough Concentration (Cmin) For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

6.  Secondary:   Apparent Oral Clearance (CL/F) For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

7.  Secondary:   Plasma Decay Half-Life (t1/2) For Axitinib: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8 hours postdose on Cycle 1 Day 8, Cycle 2 Day 1 ]

8.  Secondary:   Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

9.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

10.  Secondary:   Maximum Observed Plasma Concentration (Cmax) For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

11.  Secondary:   Minimum Observed Plasma Trough Concentration (Cmin) For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

12.  Secondary:   Clearance (CL) For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

13.  Secondary:   Plasma Decay Half-Life (t1/2) For Oxaliplatin: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

14.  Secondary:   Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

15.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

16.  Secondary:   Maximum Observed Plasma Concentration (Cmax) For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

17.  Secondary:   Minimum Observed Plasma Trough Concentration (Cmin) For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

18.  Secondary:   Clearance (CL) For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

19.  Secondary:   Plasma Decay Half-Life (t1/2) For 5-Fluorouracil: Phase 1   [ Time Frame: Pre-5-FU bolus, 5 min (post-5-FU bolus), 0.25, 0.5, 0.75, 2, 4, 6, 22, 34-46 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

20.  Secondary:   Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

21.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

22.  Secondary:   Maximum Observed Plasma Concentration (Cmax) For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

23.  Secondary:   Minimum Observed Plasma Trough Concentration (Cmin) For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

24.  Secondary:   Clearance (CL) For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

25.  Secondary:   Plasma Decay Half-Life (t1/2) For Irinotecan: Phase 1   [ Time Frame: Predose, 1, 2, 2.5, 4, 6, 8, 24 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

26.  Secondary:   Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

27.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

28.  Secondary:   Maximum Observed Plasma Concentration (Cmax) For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

29.  Secondary:   Minimum Observed Plasma Trough Concentration (Cmin) For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

30.  Secondary:   Clearance (CL) For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

31.  Secondary:   Plasma Decay Half-Life (t1/2) For Bevacizumab: Phase 1   [ Time Frame: Predose, 1, 2, 2.25, 2.5, 4, 6, 8, 24, 36-48 hours postdose on Cycle 1 Day 1, Cycle 2 Day 1 ]

32.  Secondary:   Duration of Response (DR): Phase 2   [ Time Frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) ]

33.  Secondary:   Progression-Free Survival (PFS): Phase 2   [ Time Frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) ]

34.  Secondary:   Time to Treatment Failure (TTF): Phase 2   [ Time Frame: Baseline (Phase 2) until disease progression, assessed every 6 weeks up to Week 148 (Phase 2) or follow-up (every 6 weeks after last dose of study drug until progression or start of alternate therapy) ]

35.  Secondary:   Overall Survival (OS): Phase 2   [ Time Frame: Every 3 months after discontinuation of study treatment until death due to any cause or 1 year after randomization of the last participant ]

36.  Secondary:   Change From Baseline in M.D. Anderson Symptom Assessment Inventory - Diarrhea (MDASI-D) Symptom Severity and Interference Subscale Scores at Day 1 of Cycle 2 Through Day 1 Cycle 42 and Follow-up: Phase 2   [ Time Frame: Cycle 1 Day 1 (baseline), every 2 weeks for the first 2 months (Cycle 2 Day 1 [C2D1], Cycle 3 Day 1, and Cycle 4 Day 1) then monthly thereafter starting Cycle 6 Day 1, and 28 days after the last dose ]


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  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
Time to Treatment Failure (TTF) was included as a secondary endpoint of the study after change in analysis plan.


  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: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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Publications automatically indexed to this study:

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00460603     History of Changes
Other Study ID Numbers: A4061020
Study First Received: April 13, 2007
Results First Received: March 28, 2013
Last Updated: November 7, 2013
Health Authority: United States: Food and Drug Administration