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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
  Purpose

To determine the safety and efficacy of AG-013736 in combination with other standard of care medication in patients with first line metastatic colorectal cancer.


Condition Intervention Phase
Colorectal Neoplasms
Drug: bevacizumab
Drug: AG-013726
Drug: AG-013736 (axitinib)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Combinations With Chemotherapy And Bevacizumab In Patients With Metastatic Colorectal Cancer Preceded By A Phase 1 Portion

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Percentage of participants with objective response (OR) based assessment of confirmed complete response(CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all lesions and no appearance of new lesions. Confirmed PR defined as >=30 percent (%) decrease in sum of the longest dimensions (LD) of the target lesions taking as reference the baseline sum LD , without progression of nontarget lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). Pharmacokinetic (PK) parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUClast for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

  • 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. AUC (t - ∞] for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

  • 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 ] [ Designated as safety issue: No ]
    PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3.Cmax for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data. Results were normalized to axitinib 5 mg dose.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed (F). Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. CL/F for axitinib (AG-013736) in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of axitinib (AG-013736) were combined for Cohorts 1, 2, and 3. t1/2 for axitinib in absence of bevacizumab + FOLFOX was estimated from Cycle 1 Day 8 data and in presence of bevacizumab + FOLFOX was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUClast for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

  • 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

  • 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 ] [ Designated as safety issue: No ]
    PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. Cmax for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 oxaliplatin dose.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. CL for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of oxaliplatin, assessed by estimating total platinum in plasma ultrafiltrate, were combined for Cohorts 1, 2, and 3. t1/2 for oxaliplatin in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUClast for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

  • 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

  • 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 ] [ Designated as safety issue: No ]
    PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. Cmax for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 5-FU dose.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. CL for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of 5-FU were combined for Cohorts 1, 2, and 3. t1/2 for 5-FU in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). AUClast for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

  • 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). AUC (0 - ∞) for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

  • 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 ] [ Designated as safety issue: No ]
    Cmax for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. Results were normalized to Cycle 1 Day 1 irinotecan dose.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. t1/2 for irinotecan in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUClast for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

  • 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 ] [ Designated as safety issue: No ]
    AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It was obtained from AUC (0 - t) plus AUC (t - ∞). PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. AUC (0 - ∞) for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

  • 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 ] [ Designated as safety issue: No ]
    PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. Cmax for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data. The bevacizumab pharmacokinetic parameters were normalized to 1 mg/kg dose.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    CL is a quantitative measure of the rate at which a drug substance is removed from the body. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. CL for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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 ] [ Designated as safety issue: No ]
    Plasma decay half-life (t1/2) is the time measured for the plasma concentration to decrease by one half. PK parameters of bevacizumab were combined for Cohorts 1, 2, and 3. t1/2 for bevacizumab in absence of axitinib was estimated from Cycle 1 Day 1 data and in presence of axitinib was estimated from Cycle 2 Day 1 data.

  • 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) ] [ Designated as safety issue: No ]
    Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. CR: disappearance of all lesions and no appearance of new lesions. PR: >=30% decrease in sum of LD of target lesions taking as reference the baseline sum LD, without progression of nontarget lesions and no appearance of new lesions. Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

  • 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) ] [ Designated as safety issue: No ]
    Time in days from date of randomization to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

  • 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) ] [ Designated as safety issue: No ]
    TTF is defined as the time from the randomization to the date of the first documentation of PD, symptomatic deterioration, death due to any cause, or treatment discontinuation due to adverse event, refusal or other reasons. Progression: >=20% increase in sum of LD of target lesions taking as references the smallest sum LD recorded since treatment start, unequivocal progression of existing nontarget lesions, or appearance of new lesions, occurrence of pleural effusion/ascites, substantiated by cytologic investigation.

  • 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 ] [ Designated as safety issue: No ]
    Time in days from randomization date to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

  • 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 ] [ Designated as safety issue: No ]
    PROs included assessment of symptom severity and interference which were measured using M.D. Anderson Symptom Assessment Inventory-Diarrhea (MDASI-D), 20-item questionnaire which assesses the severity of 14 symptoms over the past 24 hours, as well as symptoms interference with 6 areas of function (e.g., walking, work, mood), when the symptom was "at its worst". Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was "as bad as you can imagine" or "interfered completely" with their life. The 2 subscales, symptom severity score and symptom interference score were average of respective items and ranged from 0 to 10, higher score indicating greater severity or interference of symptoms.


Enrollment: 187
Study Start Date: January 2006
Study Completion Date: November 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
bevacizumab 5 mg/kg every 2 weeks + FOLFOX
Drug: bevacizumab
bevacizumab 5 mg/kg every 2 weeks
Experimental: C
AG-013726 5 mg bid+ bevacizumab 2 mg/kg every 2 weeks + FOLFOX
Drug: AG-013726
AG-013726 5 mg bid every 2 weeks
Experimental: A
AG-013736 5 mg bid starting dose + FOLFOX
Drug: AG-013736 (axitinib)
AG-013736 5 mg bid starting dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • (Phase 1) Patients with any solid/GI tumor who have had no more than 1 previous chemotherapy for greater than 3 months prior to enrollment
  • (Phase 2) Patients with locally advanced or metastatic colorectal cancer (CRC) previously untreated with any systemic therapy.
  • Patients treated with adjuvant chemotherapy (with radiation) will be eligible if last treatment was > 12 months prior to enrollment,
  • Patients must have measurable disease by RECIST and if any history of hypertension, it must be controlled with medication.

Exclusion Criteria:

  • Prior system therapy for advanced CRC (Ph 2 portion only)
  • Prior treatment with anti-angiogenesis agent such as bevacizumab or VEGF inhibitors.
  • Prior irradiation of greater than 25% of bone marrow (whole pelvis = 25%)
  • Prior radiation, major surgery, or investigational agent within 4 weeks of study entry except palliative radiotherapy to non-target, metastatic lesions. Minor surgeries should be completed > 2 weeks of enrollment and be fully recovered from any procedure.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00460603

  Hide Study Locations
Locations
United States, Alabama
Pfizer Investigational Site
Daphne, Alabama, United States, 36526
Pfizer Investigational Site
Huntsville, Alabama, United States, 35805
Pfizer Investigational Site
Huntsville, Alabama, United States, 35801
Pfizer Investigational Site
Mobile, Alabama, United States, 36608
United States, California
Pfizer Investigational Site
Antioch, California, United States, 94531
Pfizer Investigational Site
Colton, California, United States, 92324
Pfizer Investigational Site
Corona, California, United States, 92879
Pfizer Investigational Site
Gilroy, California, United States, 95020
Pfizer Investigational Site
Glendora, California, United States, 91741
Pfizer Investigational Site
La Jolla, California, United States, 92037
Pfizer Investigational Site
La Jolla, California, United States, 92093
Pfizer Investigational Site
LaJolla, California, United States, 92093
Pfizer Investigational Site
Pasadena, California, United States, 91105
Pfizer Investigational Site
Pleasant Hill, California, United States, 94523
Pfizer Investigational Site
Pomona, California, United States, 91767
Pfizer Investigational Site
Rancho Cucamonga, California, United States, 91730
Pfizer Investigational Site
Rancho Mirage, California, United States, 92270
Pfizer Investigational Site
Redlands, California, United States, 92374
Pfizer Investigational Site
San Diego, California, United States, 92103
Pfizer Investigational Site
San Diego, California, United States, 92121
Pfizer Investigational Site
San Leandro, California, United States, 94578
Pfizer Investigational Site
West Covina, California, United States, 91790
United States, Colorado
Pfizer Investigational Site
Auroa, Colorado, United States, 80012
Pfizer Investigational Site
Boulder, Colorado, United States, 80303
Pfizer Investigational Site
Colorado Springs, Colorado, United States, 80909
Pfizer Investigational Site
Denver, Colorado, United States, 80220
Pfizer Investigational Site
Denver, Colorado, United States, 80218
Pfizer Investigational Site
Lakewood, Colorado, United States, 80228
Pfizer Investigational Site
Littleton, Colorado, United States, 80120-4413
Pfizer Investigational Site
Lone Tree, Colorado, United States, 80124
Pfizer Investigational Site
Longmont, Colorado, United States, 80501
Pfizer Investigational Site
Parker, Colorado, United States, 80138
Pfizer Investigational Site
Thornton, Colorado, United States, 80260
United States, Florida
Pfizer Investigational Site
Ocala, Florida, United States, 34471
Pfizer Investigational Site
Stuart, Florida, United States, 34994
United States, Georgia
Pfizer Investigational Site
Atlanta, Georgia, United States, 30318
United States, Indiana
Pfizer Investigational Site
Beech Grove, Indiana, United States, 46107
Pfizer Investigational Site
Indianapolis, Indiana, United States, 46237
Pfizer Investigational Site
Jeffersonville, Indiana, United States, 47130
Pfizer Investigational Site
Muncie, Indiana, United States, 47303
United States, Kansas
Pfizer Investigational Site
Kansas City, Kansas, United States, 66112
Pfizer Investigational Site
Overland Park, Kansas, United States, 66210
United States, Kentucky
Pfizer Investigational Site
Louisville, Kentucky, United States, 40207
Pfizer Investigational Site
Louisville, Kentucky, United States, 40241
Pfizer Investigational Site
Louisville, Kentucky, United States, 40217
Pfizer Investigational Site
Louisville, Kentucky, United States, 40202
Pfizer Investigational Site
Shelbyville, Kentucky, United States, 40065
United States, Louisiana
Pfizer Investigational Site
Baton Rouge, Louisiana, United States, 70809
United States, Michigan
Pfizer Investigational Site
Brownstone, Michigan, United States, 48183
Pfizer Investigational Site
Dearborn, Michigan, United States, 48126
Pfizer Investigational Site
Detroit, Michigan, United States, 48202
Pfizer Investigational Site
West Bloomfield, Michigan, United States, 48322
United States, Missouri
Pfizer Investigational Site
Kansas City, Missouri, United States, 64111
Pfizer Investigational Site
Kansas City, Missouri, United States, 64131
Pfizer Investigational Site
Kansas City, Missouri, United States, 64154
Pfizer Investigational Site
Lee's Summit, Missouri, United States, 64064
Pfizer Investigational Site
St. Louis, Missouri, United States, 63110
United States, Nebraska
Pfizer Investigational Site
Grand Island, Nebraska, United States, 68803
United States, Nevada
Pfizer Investigational Site
Las Vegas, Nevada, United States, 89135
United States, New Jersey
Pfizer Investigational Site
Summit, New Jersey, United States, 07902
United States, New York
Pfizer Investigational Site
Albany, New York, United States, 12208
Pfizer Investigational Site
Albany, New York, United States, 12206
Pfizer Investigational Site
Amsterdam, New York, United States, 12010
Pfizer Investigational Site
Hudson, New York, United States, 12534
Pfizer Investigational Site
Latham, New York, United States, 12110-0610
Pfizer Investigational Site
Rexford, New York, United States, 12148
Pfizer Investigational Site
Troy, New York, United States, 12180
United States, North Carolina
Pfizer Investigational Site
Kernersville, North Carolina, United States, 27284
Pfizer Investigational Site
Lexington, North Carolina, United States, 27295
Pfizer Investigational Site
Mount Airy, North Carolina, United States, 27030
Pfizer Investigational Site
North Wilkesboro, North Carolina, United States, 28659
Pfizer Investigational Site
Pollocksville, North Carolina, United States, 28573
Pfizer Investigational Site
Winston Salem, North Carolina, United States, 27103
United States, Oregon
Pfizer Investigational Site
Oregon City, Oregon, United States, 97045
Pfizer Investigational Site
Portland, Oregon, United States, 97213
Pfizer Investigational Site
Portland, Oregon, United States, 97227
Pfizer Investigational Site
Portland, Oregon, United States, 97225
Pfizer Investigational Site
Tualatin, Oregon, United States, 97062
United States, Pennsylvania
Pfizer Investigational Site
West Reading, Pennsylvania, United States, 19611
United States, South Carolina
Pfizer Investigational Site
Charleston, South Carolina, United States, 29406
Pfizer Investigational Site
Easley, South Carolina, United States, 29640
Pfizer Investigational Site
Greenville, South Carolina, United States, 29605
Pfizer Investigational Site
Greenville, South Carolina, United States, 29615
Pfizer Investigational Site
Seneca, South Carolina, United States, 29672
Pfizer Investigational Site
Spartanburg, South Carolina, United States, 29307
United States, Tennessee
Pfizer Investigational Site
Chattanooga, Tennessee, United States, 37403
Pfizer Investigational Site
Franklin, Tennessee, United States, 37067
Pfizer Investigational Site
Gallatin, Tennessee, United States, 37066
Pfizer Investigational Site
Hermitage, Tennessee, United States, 37076
Pfizer Investigational Site
Lebanon, Tennessee, United States, 37087
Pfizer Investigational Site
Nashville, Tennessee, United States, 37211
Pfizer Investigational Site
Nashville, Tennessee, United States, 37205
Pfizer Investigational Site
Nashville, Tennessee, United States, 37207
Pfizer Investigational Site
Nashville, Tennessee, United States, 37203
Pfizer Investigational Site
Smyrna, Tennessee, United States, 37167
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75235
Pfizer Investigational Site
Dallas, Texas, United States, 75390
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Pfizer Investigational Site
Dallas, Texas, United States, 75237
Pfizer Investigational Site
Fort Worth, Texas, United States, 76177
Pfizer Investigational Site
Houston, Texas, United States, 77090
Pfizer Investigational Site
Tyler, Texas, United States, 75702
United States, Utah
Pfizer Investigational Site
Ogden, Utah, United States, 84403-3274
United States, Washington
Pfizer Investigational Site
Everett, Washington, United States, 98201
Pfizer Investigational Site
Kennewick, Washington, United States, 99336
Pfizer Investigational Site
Vancouver, Washington, United States, 98686
Pfizer Investigational Site
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

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

Keywords provided by Pfizer:
GI neoplasms (phase 1)

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases
Axitinib
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014