Axitinib (AG-013736) With Or Without Dose Titration (Increase) In Patients With Kidney Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00835978
First received: February 2, 2009
Last updated: August 5, 2014
Last verified: August 2014
Results First Received: October 11, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Carcinoma, Renal Cell
Intervention: Drug: 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
This study was conducted at 49 centers in Czech Republic, Germany, Japan, Russian Federation, Spain, and United States (US).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were enrolled in a 4-week lead-in period, during which they received axitinib 5 milligram (mg) twice a day (BID). After the lead-in period, participants meeting randomization criteria were then randomized to one of the two treatment arms. Participants, not meeting criteria, continued study without dose titration (non-randomized arm).

Reporting Groups
  Description
Active Titration Arm Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator’s clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
Placebo Titration Arm Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator’s clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).
Non-randomized Arm Participants not eligible for randomization were assigned to receive axitinib 5 mg BID or a reduced dose per the dose modification guideline. Dose titration was not permitted in this treatment arm.
Discontinued Prior to Randomization Participants who discontinued before they were randomized to any of the treatment or non-randomized arms.

Participant Flow:   Overall Study
    Active Titration Arm     Placebo Titration Arm     Non-randomized Arm     Discontinued Prior to Randomization  
STARTED     56     56     91     10  
Treated     56     56     91     10  
COMPLETED     0     0     0     0  
NOT COMPLETED     56     56     91     10  
Death                 21                 20                 31                 4  
Lost to Follow-up                 2                 4                 2                 0  
Not Specified                 0                 3                 4                 2  
Objective progression or relapse                 1                 1                 0                 0  
Adverse Event                 1                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 2  
Study ongoing                 31                 28                 54                 1  



  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.
The safety analysis (SA) population consists of all participants who received at least one dose of study medication.

Reporting Groups
  Description
Active Titration Arm Participants initially received axitinib 5 mg twice a day (BID) + axitinib (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + axitinib (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator’s clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + axitinib [blinded therapy] 5 mg BID).
Placebo Titration Arm Participants initially received axitinib 5mg BID + placebo (blinded therapy) 2 mg BID. After at least 2 consecutive weeks, participants satisfying the dose titration criteria had their dose level increased by one additional dose level, to axitinib 5 mg BID + placebo (blinded therapy) 5 mg BID, unless otherwise contraindicated per the investigator’s clinical judgment. The maximum total daily dose was 10 mg BID (axitinib 5mg BID + placebo [blinded therapy] 5 mg BID).
Non-randomized Arm Participants not eligible for randomization were assigned to receive axitinib 5 mg BID or a reduced dose per the dose modification guideline. Dose titration was not permitted in this treatment arm.
Discontinued Prior to Randomization Participants who discontinued before they were randomized to any of the treatment or non-randomized arms.
Total Total of all reporting groups

Baseline Measures
    Active Titration Arm     Placebo Titration Arm     Non-randomized Arm     Discontinued Prior to Randomization     Total  
Number of Participants  
[units: participants]
  56     56     91     10     213  
Age  
[units: Years]
Mean ± Standard Deviation
  59.7  ± 10.2     59.6  ± 10.5     62.9  ± 8.9     62.9  ± 7.5     61.2  ± 9.7  
Age, Customized  
[units: Number of Participants]
         
< 65 Years     38     38     54     6     136  
>= 65 Years     18     18     37     4     77  
Gender  
[units: Number of Participants]
         
Female     19     11     36     4     70  
Male     37     45     55     6     143  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Objective Response Rate (ORR) - Percentage of Participants With Objective Response   [ Time Frame: Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks. ]

2.  Secondary:   Objective Response Rate (ORR) - Percentage of Participants With Objective Response (All Participants)   [ Time Frame: Baseline up to disease progression, death, or withdrawal with minimum follow-up of 12 months; assessments performed at baseline and repeated every 8 weeks. ]

3.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ]

4.  Secondary:   Progression-Free Survival (PFS) - All Participants   [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ]

5.  Secondary:   Duration of Response (DR)   [ Time Frame: Baseline up to disease progression, death, or withdrawal; performed at baseline and repeated every 8 weeks for 24 weeks, then every 12 weeks ]

6.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Axitinib   [ Time Frame: Cycle 2 Day 15 (C2D15): pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

7.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) for Axitinib,   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

8.  Secondary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Axitinib   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

9.  Secondary:   Area Under the Curve From Time Zero to 24 Hours[AUC(0-24)] for Axitinib   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

10.  Secondary:   Plasma Decay Half-Life (t1/2) for Axitinib   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

11.  Secondary:   Apparent Oral Clearance (CL/F) of Axitinib   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

12.  Secondary:   Apparent Volume of Distribution During the Elimination Phase (Vz/F) for Axitinib   [ Time Frame: C2D15: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose ]

13.  Secondary:   Change From Baseline in Systolic Blood Pressure   [ Time Frame: Baseline up to follow-up visit ]

14.  Secondary:   Change From Baseline in Diastolic Blood Pressure   [ Time Frame: Baseline up to follow-up visit ]

15.  Secondary:   Comparison of Circulating Endothelial Cells (CECs) in Blood: Cluster of Differentiation (CD)146+/CD105+ at Baseline   [ Time Frame: Baseline ]

16.  Secondary:   Comparison of the Ratio of CECs in Blood: CD146+/CD105+ at Each Time Point to Baseline   [ Time Frame: Cycle 1 Day 1 (C1D1), C1D15, C2D15, End of therapy (EOT) ]

17.  Secondary:   Circulating Endothelial Cells (CECs) in Blood: CD31+/CD146+   [ Time Frame: Baseline ]

18.  Secondary:   Comparison of Ratio of CECs in Blood: CD31+/CD146+ at Each Time Point to Baseline   [ Time Frame: C1D1, C1D15, C2D15, EOT ]

19.  Secondary:   ORR in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms   [ Time Frame: Baseline, C1D1 ]

20.  Secondary:   PFS in Subgroups That Were Defined by Vascular Endothelial Growth Factor A (VEGFA) or Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Polymorphisms   [ Time Frame: Baseline, C1D1 ]

21.  Secondary:   Overall Survival (OS)   [ Time Frame: Baseline up to at least one year after the last patient has been randomized. ]
Results not yet posted.   Anticipated Posting Date:   01/2015   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided by Pfizer

Publications automatically indexed to this study:

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00835978     History of Changes
Other Study ID Numbers: A4061046
Study First Received: February 2, 2009
Results First Received: October 11, 2013
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration