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)

Study Overview

• Status: Completed
• Conditions: Carcinoma, Renal Cell
• Intervention / Treatment: Drug: AG-013736

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-8543
    • Akita University Hospital
  • Fukuoka, Japan, 811-1395
    • National Kyushu Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital, Department of Urology
  • Kyoto, Japan, 602-8566
    • University Hospital, Kyoto Prefectural University of Medicine
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospotal
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center East Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • Tsukuba University Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University
  • Kochi-ken
    • Nankoku-shi, Kochi-ken, Japan, 783-8505
      • Kochi Medical School Hospital
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kinki University Hospital
  • Shizuoka
    • Hamamatsu-City, Shizuoka, Japan, 431-3192
      • Hamamatsu University School of Medicine University Hospital
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Arakawa-ku, Tokyo, Japan, 116-8567
      • Tokyo Women's Medical University Medical Center East
    • Chuo-ku, Tokyo, Japan, 104-8503
      • National Cancer Center
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 765 days of treatment at the data cut-off date
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.	Up to 765 days of treatment at the data cut-off date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]).	Up to 1709 days of treatment
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]).	Up to 1709 days of treatment
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.	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.
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.	Up to 2002 days (maximum duration of treatment plus follow-up observation)
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.	Cycle 1 Day 1 (2 hours after morning dose); Cycles 3, 5, and 7 Day 1 predose and 2 hours post morning dose
Plasma Concentration of Soluble Vascular Endothelial Growth Factor Receptor 1 (s-VEGFR1)		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)		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)		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)		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)		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	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.	Up to 1709 days of treatment plus 28-days follow-up

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2007
• Primary Completion (Actual): February 26, 2010
• Study Completion (Actual): October 30, 2012

Study Registration Dates

• First Submitted: December 7, 2007
• First Submitted That Met QC Criteria: December 7, 2007
• First Posted (Estimate): December 10, 2007

Study Record Updates

• Last Update Posted (Actual): June 5, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Phase 2; RCC; AG-013736
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: A4061035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.