Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine For Advanced Pancreatic Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00471146
First received: May 7, 2007
Last updated: June 14, 2012
Last verified: June 2012
Results First Received: February 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Carcinoma, Pancreatic Ductal
Interventions: Drug: AG-013736
Drug: Gemcitabine
Drug: placebo

  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
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) in cycles of 4 weeks. Gemcitabine 1000 mg per square meter (mg/m^2) 30 minutes intravenous (IV) infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Participant Flow:   Overall Study
    Axitinib + Gemcitabine     Placebo + Gemcitabine  
STARTED     314     316  
Treated     305     308  
COMPLETED     142     142  
NOT COMPLETED     172     174  
Adverse Event                 32                 33  
Withdrawal by Subject                 14                 11  
Death                 11                 12  
Lost to Follow-up                 4                 2  
Protocol Violation                 2                 2  
Objective progression or relapse                 84                 87  
Global deterioration of health status                 12                 14  
Randomized but not treated                 9                 8  
Unspecified                 4                 5  



  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
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Total Total of all reporting groups

Baseline Measures
    Axitinib + Gemcitabine     Placebo + Gemcitabine     Total  
Number of Participants  
[units: participants]
  314     316     630  
Age, Customized  
[units: Participants]
     
Less than 65 years     203     179     382  
Greater than or equal to 65 years     111     137     248  
Gender  
[units: Participants]
     
Female     123     128     251  
Male     191     188     379  



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]

2.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Baseline until disease progression or at least 1 year after the randomization of last participant ]

3.  Secondary:   Percentage of Participants With Objective Response (OR)   [ Time Frame: Baseline, every 8 weeks until tumor progression or death ]

4.  Secondary:   Duration of Response (DR)   [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]

5.  Secondary:   Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

6.  Secondary:   Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

7.  Secondary:   Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

8.  Secondary:   Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile
Measure Description EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time Frame Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal  
Safety Issue No  

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.
ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or received a different drug from that to which they were randomized.

Reporting Groups
  Description
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Measured Values
    Axitinib + Gemcitabine     Placebo + Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  314     316  
Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile  
[units: Units on a scale]
Mean ± Standard Deviation
   
Baseline (n=289, 290)     0.665  ± 0.2709     0.690  ± 0.2479  
Change at C2 D1 (n=231, 240)     0.050  ± 0.2699     0.020  ± 0.2033  
Change at C3 D1 (n=171, 178)     0.053  ± 0.2528     0.028  ± 0.2362  
Change at C4 D1 (n=128, 131)     0.010  ± 0.2730     0.050  ± 0.2209  
Change at C5 D1 (n=94, 80)     0.010  ± 0.2889     0.044  ± 0.2092  
Change at C6 D1 (n=57, 57)     0.001  ± 0.2489     0.058  ± 0.2294  
Change at C7 D1 (n=37, 36)     0.049  ± 0.1891     0.075  ± 0.1838  
Change at C8 D1 (n=17, 20)     -0.021  ± 0.2366     0.071  ± 0.2188  
Change at C9 D1 (n=9, 9)     0.049  ± 0.1878     0.121  ± 0.3006  
Change at C10 D1 (n=3, 4)     0.181  ± 0.2206     0.208  ± 0.3034  
Change at C11 D1 (n=1, 1)     0.000  ± NA [1]   0.058  ± NA [1]
Change at C12 D1 (n=1, 0)     0.000  ± NA [1]   NA  ± NA [2]
Change at C13 D1 (n=1, 1)     0.000  ± NA [1]   0.470  ± NA [1]
Change at follow-up (n=65, 73)     -0.148  ± 0.3637     -0.080  ± 0.3243  
[1] Standard deviation was not estimable since only one participant was evaluable.
[2] Data was not analyzed as no participants were evaluable for the particular cycle.

No statistical analysis provided for Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile



9.  Secondary:   Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

10.  Secondary:   Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)   [ Time Frame: Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 23 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


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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
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