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

• ClinicalTrials.gov Identifier: NCT00569946
• Recruitment Status: Completed
• First Posted: December 10, 2007
• Results First Posted: March 27, 2012
• Last Update Posted: June 5, 2019
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: December 7, 2007
• First Posted Date: December 10, 2007
• Results First Submitted Date: February 25, 2012
• Results First Posted Date: March 27, 2012
• Last Update Posted Date: June 5, 2019
• Actual Study Start Date: December 12, 2007
• Actual Primary Completion Date: February 26, 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 16, 2014)

• 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 ]
  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 ]
  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.

• Original Primary Outcome Measures (submitted: December 7, 2007): Investigate objective tumor response of AG-013736 for metastic Renal Cell Cancer (mRCC) [ Time Frame: End of study ]

Current Secondary Outcome Measures (submitted: July 16, 2014)

• Progression-Free Survival (PFS) [ Time Frame: Up to 1709 days of treatment ]
  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 ]
  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. ]
  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) ]
  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 ]
  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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• Number of Participants With Adverse Events [ Time Frame: Up to 1709 days of treatment plus 28-days follow-up ]
  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.

Original Secondary Outcome Measures (submitted: December 7, 2007)

• 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 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Of AG-013736 (Axitinib) As Second-Line Treatment In Patients With Metastatic Renal Cell Cancer (mRCC)
• Official Title: PHASE 2 STUDY OF AG-013736 AS SECOND-LINE TREATMENT IN PATIENTS WITH METASTATIC RENAL CELL CANCER
• Brief Summary: To investigate objective tumor response of AG-013736 for metastatic Renal Cell Cancer (mRCC)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Renal Cell

Intervention

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.

Study Arms

Experimental: AG-013736

Intervention: Drug: AG-013736

Publications *

• Schindler E, Amantea MA, Karlsson MO, Friberg LE. A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients. CPT Pharmacometrics Syst Pharmacol. 2017 Jun;6(6):373-382. doi: 10.1002/psp4.12193. Epub 2017 May 26.
• Eto M, Uemura H, Tomita Y, Kanayama H, Shinohara N, Kamei Y, Fujii Y, Umeyama Y, Ozono S, Naito S, Akaza H; Japan Axitinib Phase II Study Group. Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma. Cancer Sci. 2014 Dec;105(12):1576-83. doi: 10.1111/cas.12546. Epub 2014 Nov 25.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 16, 2012): 64
• Original Estimated Enrollment (submitted: December 7, 2007): 63
• Actual Study Completion Date: October 30, 2012
• Actual Primary Completion Date: February 26, 2010 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00569946
• Other Study ID Numbers: A4061035
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2019