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Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00282048
Recruitment Status : Completed
First Posted : January 25, 2006
Results First Posted : April 3, 2012
Last Update Posted : July 31, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE January 23, 2006
First Posted Date  ICMJE January 25, 2006
Results First Submitted Date  ICMJE February 25, 2012
Results First Posted Date  ICMJE April 3, 2012
Last Update Posted Date July 31, 2012
Study Start Date  ICMJE March 2006
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2012)
Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks ]
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 responses. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.
Original Primary Outcome Measures  ICMJE
 (submitted: January 23, 2006)
To determine the activity and response rate of AG-013736 in patients with advanced and refractory renal cell cancer as measured by overall objective response rate, CR and PR, by RECIST.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2012)
  • Progression-free Survival (PFS) [ Time Frame: Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 152 weeks ]
    Time in days from start of study treatment 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").
  • Duration of Response (DR) [ Time Frame: Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks ]
    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.
  • Overall Survival (OS) [ Time Frame: Baseline to death due to any cause or at least 1 year after the first dose for the last participant ]
    Time in days from the start of study treatment 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 AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
  • Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index for Disease Cancer Related Symptoms (FKSI-DRS) Score [ Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose) ]
    FKSI-DRS is a subset of FKSI which is a questionnaire for FACT -Kidney Symptom Index used to assess Quality of Life (QoL)/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions and the FKSI-DRS consisted of 9 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI-DRS ranged between 0-36. Since the questions could be reversed coded, as appropriate, before calculating FKSI-DRS, 0 and 36 could be considered the worst and best health states based on the 9 questions comprising FKSI-DRS.
  • Population Pharmacokinetics of Axitinib (AG-013736) [ Time Frame: Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks ]
    Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2006)
Safety profile of AG-013736; progression-free survival, duration of response; overall survival; explore effects of treatment on patient reported outcomes; cancer related symptoms (FKSI); explore PK correlates with response or adverse events.
Current Other Pre-specified Outcome Measures
 (submitted: July 23, 2012)
  • Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) Score [ Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose) ]
    FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.
  • Correlation of Area Under the Concentration-time Curve at Steady State (AUCss) With Confirmed Partial Response (PR) [ Time Frame: Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks ]
    AUCss: pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods, computed as each participant's average total daily dose (accounting for dose reductions and any recorded missed doses) divided by population estimated posthoc individual apparent clearance (CL/F), i.e., AUCss = Daily Dose/(CL/F), where F refers to the oral bioavailability, and CL refers to the systemic clearance. PR: responses with at least 30% decrease in sum of longest dimensions of target lesions using baseline (pre-treatment) sum of longest dimensions as reference. Logistic regression with general linear model was applied to data of PR using AUCss; PR was correlated with AUCss as fold increase in odds of PR with increase in AUCss. Fold increase was calculated as exponent of product of logistic regression slope coefficient and unit change of AUCss.
  • Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Progression-free Survival (PFS) [ Time Frame: Day 1 (Pre-dose), Day 29, and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks ]
    AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. PFS is median time from first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Relationship of PFS versus AUCss was determined as median PFS in participants with high AUCss [AUCss greater than or equal to (>=) median AUCss] or low AUCss [AUCss less than (<) median AUCss].
  • Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Overall Survival (OS) [ Time Frame: Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks ]
    AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. OS is time in weeks from the start of study treatment to date of death due to any cause. Relationship of OS versus AUCss was determined as median OS in participants with high AUCss [AUCss >= median AUCss] or low AUCss [AUCss < median AUCss].
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer
Official Title  ICMJE Phase 2 Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer
Brief Summary To determine the activity and response rate of AG-013736 in patients with advanced and refractory renal cell cancer, (patients who also failed on sorafenib-based therapy).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Kidney Neoplasms
  • Carcinoma, Renal Cell
Intervention  ICMJE Drug: AG-013736 (axitinib)
AG-013736 5 mg twice daily [bid] continuous dosing in 28 day cycles.
Study Arms  ICMJE Experimental: AG-013736 (axitinib)
AG-013736 single agent in continuous dosing until disease progression or unacceptable toxicity
Intervention: Drug: AG-013736 (axitinib)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 21, 2007)
62
Original Enrollment  ICMJE
 (submitted: January 23, 2006)
32
Actual Study Completion Date  ICMJE June 2009
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • RCC with metastases and nephrectomy
  • failure of prior sorafenib-based therapy
  • at least 1 target lesion that has not been irradiated
  • adequate bone marrow, hepatic and renal function, > or equal to 18 years of age.

Exclusion Criteria:

  • Gastrointestinal abnormalities
  • current use or inability to avoid chronic antacid therapy
  • current use or anticipated inability to avoid potent CYP3A4 inhibitors or CYP1A2 inducers
  • active seizure disorder or evidence of brain metastases.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00282048
Other Study ID Numbers  ICMJE A4061023
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP