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

Study Overview
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Brief Summary
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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).

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

Conditions
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Kidney Neoplasms, Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: AG-013736 (axitinib)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |