Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer

Phase 2 Study Of AG-013736 In Patients With Refractory Metastatic Renal Cell Cancer

To determine the activity and response rate of AG-013736 in patients with advanced and refractory renal cell cancer, (patients who also failed on sorafenib-based therapy).

Study Overview

• Status: Completed
• Conditions: Kidney Neoplasms; Carcinoma, Renal Cell
• Intervention / Treatment: Drug: AG-013736 (axitinib)

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Pfizer Investigational Site
  • New York
    • Bronx, New York, United States, 10466
      • Pfizer Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Pfizer Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Pfizer Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• RCC with metastases and nephrectomy
• failure of prior sorafenib-based therapy
• at least 1 target lesion that has not been irradiated
• adequate bone marrow, hepatic and renal function, > or equal to 18 years of age.

Exclusion Criteria:

• Gastrointestinal abnormalities
• current use or inability to avoid chronic antacid therapy
• current use or anticipated inability to avoid potent CYP3A4 inhibitors or CYP1A2 inducers
• active seizure disorder or evidence of brain metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AG-013736 (axitinib); AG-013736 single agent in continuous dosing until disease progression or unacceptable toxicity	Drug: AG-013736 (axitinib); AG-013736 5 mg twice daily [bid] continuous dosing in 28 day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of responses. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.	Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").	Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 152 weeks
Duration of Response (DR)	Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. 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. DR was calculated for the subgroup of participants with a confirmed objective tumor response.	Baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 152 weeks
Overall Survival (OS)	Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.	Baseline to death due to any cause or at least 1 year after the first dose for the last participant
Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index for Disease Cancer Related Symptoms (FKSI-DRS) Score	FKSI-DRS is a subset of FKSI which is a questionnaire for FACT -Kidney Symptom Index used to assess Quality of Life (QoL)/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions and the FKSI-DRS consisted of 9 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI-DRS ranged between 0-36. Since the questions could be reversed coded, as appropriate, before calculating FKSI-DRS, 0 and 36 could be considered the worst and best health states based on the 9 questions comprising FKSI-DRS.	Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)
Population Pharmacokinetics of Axitinib (AG-013736)	Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.	Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index (FKSI) Score	FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.	Baseline (Day 1 of Cycle 1), Day 1 of all subsequent cycles up to Cycle 38 and follow up (28 days after last dose)
Correlation of Area Under the Concentration-time Curve at Steady State (AUCss) With Confirmed Partial Response (PR)	AUCss: pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods, computed as each participant's average total daily dose (accounting for dose reductions and any recorded missed doses) divided by population estimated posthoc individual apparent clearance (CL/F), i.e., AUCss = Daily Dose/(CL/F), where F refers to the oral bioavailability, and CL refers to the systemic clearance. PR: responses with at least 30% decrease in sum of longest dimensions of target lesions using baseline (pre-treatment) sum of longest dimensions as reference. Logistic regression with general linear model was applied to data of PR using AUCss; PR was correlated with AUCss as fold increase in odds of PR with increase in AUCss. Fold increase was calculated as exponent of product of logistic regression slope coefficient and unit change of AUCss.	Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks
Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Progression-free Survival (PFS)	AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. PFS is median time from first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Relationship of PFS versus AUCss was determined as median PFS in participants with high AUCss [AUCss greater than or equal to (>=) median AUCss] or low AUCss [AUCss less than (<) median AUCss].	Day 1 (Pre-dose), Day 29, and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks
Relationship of Area Under the Concentration-time Curve at Steady State (AUCss) With Overall Survival (OS)	AUCss is a pharmacokinetic parameter derived from plasma concentration versus time data using non-compartmental or population based analysis methods. OS is time in weeks from the start of study treatment to date of death due to any cause. Relationship of OS versus AUCss was determined as median OS in participants with high AUCss [AUCss >= median AUCss] or low AUCss [AUCss < median AUCss].	Day 1 (Pre-dose), Day 29 and then every 8 weeks until disease progression or discontinuation from study or up to 152 weeks

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: January 23, 2006
• First Submitted That Met QC Criteria: January 23, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Estimate): July 31, 2012
• Last Update Submitted That Met QC Criteria: July 23, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• 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: A4061023