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

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

Official Title
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PHASE 2 STUDY OF AG-013736 AS SECOND-LINE TREATMENT IN PATIENTS WITH METASTATIC RENAL CELL CANCER

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: AG-013736


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AG-013736<br> | Drug: AG-013736<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AG-013736, Phase 2, RCC