search
Back to results

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

Primary Purpose

Carcinoma, Renal Cell

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
AG-013736
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring AG-013736, RCC, Phase 2

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • National Cancer Center East Hospital
  • Hokkaido University Hospital
  • Tsukuba University Hospital
  • Iwate Medical University
  • Kochi Medical School Hospital
  • Kinki University Hospital
  • Hamamatsu University School of Medicine University Hospital
  • Shizuoka Cancer Center
  • Tokyo Women's Medical University Medical Center East
  • National Cancer Center
  • Nihon University Itabashi Hospital
  • Akita University Hospital
  • National Kyushu Cancer Center
  • Kyushu University Hospital, Department of Urology
  • University Hospital, Kyoto Prefectural University of Medicine
  • Osaka University Hospital
  • Tokushima University Hospotal
  • Yamagata University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AG-013736

Arm Description

Outcomes

Primary Outcome Measures

Objective Response Rate (Percentage of Participants With Complete Response [CR] or Partial Response [PR]): Independent Review Committee Assessment
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
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 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 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 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)
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
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)
Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 2 (s-VEGFR2)
Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 3 (s-VEGFR3)
Plasma Concentration of Soluble Stem Cell Factor Receptor (s-KIT)
Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)
Number of Participants With Adverse Events
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.

Full Information

First Posted
December 7, 2007
Last Updated
May 22, 2019
Sponsor
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT00569946
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
December 12, 2007 (Actual)
Primary Completion Date
February 26, 2010 (Actual)
Study Completion Date
October 30, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
AG-013736, RCC, Phase 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AG-013736
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AG-013736
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective Response Rate (Percentage of Participants With Complete Response [CR] or Partial Response [PR]): Independent Review Committee Assessment
Description
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.
Time Frame
Up to 765 days of treatment at the data cut-off date
Title
Objective Response Rate (Percentage of Participants With Complete Response [CR] or Partial Response [PR]): Investigators Assessment
Description
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.
Time Frame
Up to 765 days of treatment at the data cut-off date
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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 Frame
Up to 1709 days of treatment
Title
Time to Tumor Progression (TTP)
Description
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]).
Time Frame
Up to 1709 days of treatment
Title
Duration of Response
Description
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.
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.
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to 2002 days (maximum duration of treatment plus follow-up observation)
Title
Number of Participants Analyzed for Population Pharmacokinetics of AG-013736
Description
Population pharmacokinetic analysis of AG-013736 is conducted by combining current study data with other AG-013736 studies.
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
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
Number of Participants With Adverse Events
Description
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.
Time Frame
Up to 1709 days of treatment plus 28-days follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
National Cancer Center East Hospital
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Tsukuba University Hospital
City
Tsukuba
State/Province
Ibaraki
ZIP/Postal Code
305-8576
Country
Japan
Facility Name
Iwate Medical University
City
Morioka
State/Province
Iwate
ZIP/Postal Code
020-8505
Country
Japan
Facility Name
Kochi Medical School Hospital
City
Nankoku-shi
State/Province
Kochi-ken
ZIP/Postal Code
783-8505
Country
Japan
Facility Name
Kinki University Hospital
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Hamamatsu University School of Medicine University Hospital
City
Hamamatsu-City
State/Province
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
Shizuoka Cancer Center
City
Sunto-gun
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan
Facility Name
Tokyo Women's Medical University Medical Center East
City
Arakawa-ku
State/Province
Tokyo
ZIP/Postal Code
116-8567
Country
Japan
Facility Name
National Cancer Center
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-8503
Country
Japan
Facility Name
Nihon University Itabashi Hospital
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Akita University Hospital
City
Akita
ZIP/Postal Code
010-8543
Country
Japan
Facility Name
National Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Kyushu University Hospital, Department of Urology
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
University Hospital, Kyoto Prefectural University of Medicine
City
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
Osaka University Hospital
City
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Tokushima University Hospotal
City
Tokushima
ZIP/Postal Code
770-8503
Country
Japan
Facility Name
Yamagata University Hospital
City
Yamagata
ZIP/Postal Code
990-9585
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
28378918
Citation
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.
Results Reference
derived
PubMed Identifier
25283266
Citation
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.
Results Reference
derived
PubMed Identifier
21889330
Citation
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4061035&StudyName=Study%20Of%20AG-013736%20%28Axitinib%29%20As%20Second-Line%20Treatment%20In%20Patients%20With%20Metastatic%20Renal%20Cell%20Cancer%20%28mRCC%29%0A
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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

We'll reach out to this number within 24 hrs