Study Of AG-013736 (Axitinib) As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer (mRCC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00569946
First received: December 7, 2007
Last updated: July 16, 2014
Last verified: July 2014

December 7, 2007
July 16, 2014
December 2007
February 2010   (final data collection date for primary outcome measure)
  • Objective Response Rate (Percentage of Participants With Complete Response [CR] or Partial Response [PR]): Independent Review Committee Assessment [ Time Frame: Up to 765 days of treatment at the data cut-off date ] [ Designated as safety issue: No ]
    Percentage of participants with objective response based assessment of confirmed CR or confirmed PR by the Independent Review Committee, according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). CR was defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks.
  • Objective Response Rate (Percentage of Participants With Complete Response [CR] or Partial Response [PR]): Investigators Assessment [ Time Frame: Up to 765 days of treatment at the data cut-off date ] [ Designated as safety issue: No ]
    Percentage of participants with objective response based assessment of confirmed CR or confirmed PR by the investigator, according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.0). CR was defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks.
Investigate objective tumor response of AG-013736 for metastic Renal Cell Cancer (mRCC) [ Time Frame: End of study ]
Complete list of historical versions of study NCT00569946 on ClinicalTrials.gov Archive Site
  • Progression-Free Survival (PFS) [ Time Frame: Up to 1709 days of treatment ] [ Designated as safety issue: No ]
    Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
  • Time to Tumor Progression (TTP) [ Time Frame: Up to 1709 days of treatment ] [ Designated as safety issue: No ]
    Time in months from start of study treatment to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
  • Duration of Response [ Time Frame: Start of first confirmed CR or PR to the date of the first event (PD or death) or the last tumor assessment, whichever came first, assessed up to 1709 days. ] [ Designated as safety issue: No ]
    Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. 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) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
  • Overall Survival (OS) [ Time Frame: Up to 2002 days (maximum duration of treatment plus follow-up observation) ] [ Designated as safety issue: No ]

    OS was defined as the time from date of first dose of AG-013736 to date of death due to any cause.

    Subjects in whom death is not reported will have their event time censored on the last date the subject is known to be alive.

  • Number of Participants Analyzed for Population Pharmacokinetics of AG-013736 [ Time Frame: Cycle 1 Day 1 (2 hours after morning dose); Cycles 3, 5, and 7 Day 1 predose and 2 hours post morning dose ] [ Designated as safety issue: No ]
    Population pharmacokinetic analysis of AG-013736 is conducted by combining current study data with other AG-013736 studies.
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 1 (s-VEGFR1) [ Time Frame: Cycle 1 Day 1 predose, Day 1 of Cycle 2 to Cycle 7, and end of treatment/discontinuation (assessed up to 1709 days) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (s-VEGFR2) [ Time Frame: Cycle 1 Day 1 predose, Day 1 of Cycle 2 to Cycle 7, and end of treatment/discontinuation (assessed up to 1709 days) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (s-VEGFR3) [ Time Frame: Cycle 1 Day 1 predose, Day 1 of Cycle 2 to Cycle 7, and end of treatment/discontinuation (assessed up to 1709 days) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Soluble Stem Cell Factor Receptor (s-KIT) [ Time Frame: Cycle 1 Day 1 predose, Day 1 of Cycle 2 to Cycle 7, and end of treatment/discontinuation (assessed up to 1709 days) ] [ Designated as safety issue: No ]
  • Plasma Concentration of Vascular Endothelial Growth Factor (VEGF) [ Time Frame: Cycle 1 Day 1 predose, Day 1 of Cycle 2 to Cycle 7, and end of treatment/discontinuation (assessed up to 1709 days) ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: Up to 1709 days of treatment plus 28-days follow-up ] [ Designated as safety issue: Yes ]
    Number of participants with any adverse events, adverse events graded as Common Terminology Criteria (CTCAE) for Adverse Events Version 3.0 Grade 3 or higher , serious adverse events, or adverse events resulted in discontinuation.
  • Progression-free survival [ Time Frame: End of study ]
  • Time to progression [ Time Frame: End of study ]
  • Duration of response [ Time Frame: End of study ]
  • Overall survival [ Time Frame: At least 3 years ]
  • Adverse Events and abnormal change of laboratory test date [ Time Frame: End of study ]
  • Plasma PK of AG-013736 [ Time Frame: End of study ]
  • Plasma concentration of s-VEGFR1, s-VEGFR2, s-VEGFR3, s-KIT and VEGF [ Time Frame: End of study ]
Not Provided
Not Provided
 
Study Of AG-013736 (Axitinib) As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer (mRCC)
Phase 2 Study Of AG-013736 As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer

To investigate objective tumor response of AG-013736 for metastatic Renal Cell Cancer (mRCC)

Not Provided
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Renal Cell
Drug: AG-013736

AG-013736 5 mg BID will be administered orally on continuous schedule. Cycle length is 28 days. If the drug is well tolerated at 5 mg BID, the dose of AG-013736 may be titrated to 7 mg BID and then to a maximum of 10 mg BID.

Number of cycles: until progression or unacceptable toxicity develops.

Experimental: AG-013736
Intervention: Drug: AG-013736
Tomita Y, Uemura H, Fujimoto H, Kanayama HO, Shinohara N, Nakazawa H, Imai K, Umeyama Y, Ozono S, Naito S, Akaza H; Japan Axitinib Phase II Study Group. Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell Carcinoma. Eur J Cancer. 2011 Nov;47(17):2592-602. doi: 10.1016/j.ejca.2011.07.014. Epub 2011 Aug 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
64
August 2013
February 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients histologically diagnosed as metastatic renal cell cancer with a component of clear cell cancer.
  • Patients who are refractory to cytokine therapy as 1st line.
  • Patients who experienced nephrectomy.
  • Patients with at least 1 target lesion, as defined by RECIST.
  • Patients with no uncontrolled hypertension.

Exclusion Criteria:

  • Gastrointestinal abnormalities
  • Current use or anticipated inability to avoid potent CYP3A4 inhibitors or CYP1A2/3A4 inducers.
  • Active seizure disorder or evidence of brain metastases.
  • Patients with hemoptysis.
Both
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00569946
A4061035
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
July 2014

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