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
  Purpose

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


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: AG-013736
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study Of AG-013736 As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 64
Study Start Date: December 2007
Study Completion Date: August 2013
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AG-013736 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.


  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569946

Locations
Japan
Pfizer Investigational Site
Kashiwa, Chiba, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
Pfizer Investigational Site
Tsukuba, Ibaraki, Japan
Pfizer Investigational Site
Morioka, Iwate, Japan
Pfizer Investigational Site
Nankoku-shi, Kochi-ken, Japan
Pfizer Investigational Site
Osakasayama, Osaka, Japan
Pfizer Investigational Site
Hamamatsu-City, Shizuoka, Japan
Pfizer Investigational Site
Sunto-gun, Shizuoka, Japan
Pfizer Investigational Site
Arakawa-ku, Tokyo, Japan
Pfizer Investigational Site
Chuo-ku, Tokyo, Japan
Pfizer Investigational Site
Itabashi-ku, Tokyo, Japan
Pfizer Investigational Site
Akita, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Kyoto, Japan
Pfizer Investigational Site
Osaka, Japan
Pfizer Investigational Site
Tokushima, Japan
Pfizer Investigational Site
Yamagata, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00569946     History of Changes
Other Study ID Numbers: A4061035
Study First Received: December 7, 2007
Results First Received: February 25, 2012
Last Updated: July 16, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Pfizer:
AG-013736
RCC
Phase 2

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014