AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00219557
First received: September 13, 2005
Last updated: July 23, 2012
Last verified: July 2012
Results First Received: February 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Pancreatic Neoplasms
Interventions: Drug: Gemcitabine
Drug: AG-013736

  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
No text entered.

Reporting Groups
  Description
Axitinib + Gemcitabine (Phase 1 Lead-In) Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily (BID) starting from Day 3 of Cycle 1, in cycles of 4 weeks. Gemcitabine 1000 milligram/square meter (mg/m^2) 30 minutes intravenous (IV) infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Axitinib + Gemcitabine Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, 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.
Gemcitabine Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Participant Flow for 2 periods

Period 1:   Phase 1
    Axitinib + Gemcitabine (Phase 1 Lead-In)     Axitinib + Gemcitabine     Gemcitabine  
STARTED     8     0     0  
COMPLETED     1     0     0  
NOT COMPLETED     7     0     0  
Lack of Efficacy                 3                 0                 0  
Adverse Event                 2                 0                 0  
Withdrawal by Subject                 1                 0                 0  
Started chemotherapy at other institute                 1                 0                 0  

Period 2:   Phase 2
    Axitinib + Gemcitabine (Phase 1 Lead-In)     Axitinib + Gemcitabine     Gemcitabine  
STARTED     0     69     34  
Treated     0     68     31  
COMPLETED     0     0     1  
NOT COMPLETED     0     69     33  
Lack of Efficacy                 0                 21                 15  
Adverse Event                 0                 22                 2  
Death                 0                 8                 2  
Unspecified                 0                 8                 6  
Withdrawal by Subject                 0                 9                 5  
Treatment not received                 0                 1                 3  



  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 (Phase 1 Lead-In) Axitinib (AG-013736) 5 milligram (mg) tablet orally twice daily (BID) starting from Day 3 of Cycle 1, in cycles of 4 weeks. Gemcitabine 1000 milligram/square meter (mg/m^2) 30 minutes intravenous (IV) infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Axitinib + Gemcitabine Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, 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.
Gemcitabine Gemcitabine 1000 mg/m^2 30 minutes 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 (Phase 1 Lead-In)     Axitinib + Gemcitabine     Gemcitabine     Total  
Number of Participants  
[units: participants]
  8     69     34     111  
Age, Customized  
[units: Participants]
       
18 years to 44 years     0     2     4     6  
45 years to 64 years     5     31     20     56  
Greater than or equal to 65 years     3     36     10     49  
Gender  
[units: Participants]
       
Female     1     34     18     53  
Male     7     35     16     58  



  Outcome Measures
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1.  Primary:   Overall Survival (OS)   [ Time Frame: Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant ]

2.  Secondary:   Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT)   [ Time Frame: Phase 1 baseline up to Week 4 ]

3.  Secondary:   Dose Confirmation of Gemcitabine on Basis of Number of Participants With Dose Limiting Toxicity (DLT)   [ Time Frame: Phase 1 Baseline up to Week 4 ]

4.  Secondary:   Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)   [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hours (hr) post-dose on Day 15 of Phase 1 Cycle 1 ]

5.  Secondary:   Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Axitinib (AG-013736)   [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Pase 1 Cycle 1 ]

6.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib (AG-013736)   [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1 ]

7.  Secondary:   Plasma Decay Half-life (t1/2) of Axitinib (AG-013736)   [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1 ]

8.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Gemcitabine   [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1 ]

9.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Gemcitabine   [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1 ]

10.  Secondary:   Plasma Decay Half-life (t1/2) of Gemcitabine   [ Time Frame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1 ]

11.  Secondary:   Percentage of Participants With Overall Response (OR)   [ Time Frame: Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks ]
  Hide Outcome Measure 11

Measure Type Secondary
Measure Title Percentage of Participants With Overall Response (OR)
Measure Description Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.
Time Frame Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks  
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.
Phase 2 ITT population included all participants randomized with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or a drug different from that to which they were randomized.

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

Measured Values
    Axitinib + Gemcitabine     Gemcitabine  
Number of Participants Analyzed  
[units: participants]
  69     34  
Percentage of Participants With Overall Response (OR)  
[units: Percentage¬†of¬†Participants]
Number ( 95% Confidence Interval )
  7.2  
  ( 2.4 to 16.1 )  
  2.9  
  ( 0.1 to 15.3 )  


Statistical Analysis 1 for Percentage of Participants With Overall Response (OR)
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] 0.661
Difference in response rate [4] 4.3
95% Confidence Interval ( -4.0 to 12.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Difference in percent of participants with overall response expressed as response rate, was used for calculation of 95% confidence interval (CI).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
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12.  Secondary:   Duration of Response (DR)   [ Time Frame: Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks ]

13.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: Phase 2 baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 80 weeks ]

14.  Secondary:   One Year Survival Probability   [ Time Frame: Phase 2 baseline to disease progression or death due to any cause or at least 1 year after the first dose for the last participant ]

15.  Secondary:   Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score at Day 1 of Every Cycle and End of Study   [ Time Frame: Phase 2 baseline [Day (D)1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS). ]

16.  Secondary:   Change From Baseline in 26-item Pancreatic Cancer-specific Quality of Life Questionnaire (QLQ-PAN26) Score at Day 1 of Every Cycle and End of Study   [ Time Frame: Phase 2 baseline [Day (D) 1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS). ]

17.  Secondary:   Population Pharmacokinetics of Axitinib (AG-013736) in Phase 2   [ Time Frame: Phase 2 Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 80 weeks ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  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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