Study Of AG-013736 (Axitinib) In Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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To evaluate the clinically recommended dose of AG-013736 (Axitinib) in Japanese patients by reviewing the safety of AG-013736 (Axitinib) following single and multiple dosing.

Official Title
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A Phase 1 Study Of AG-013736 (Axitinib) In Japanese Patients With Advanced Solid Tumors

Conditions
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Carcinoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients histologically or cytologically diagnosed with advanced malignant solid tumors Patients for whom standard therapies have not been effective, or for whom there are no suitable therapies Exclusion Criteria: Central lung lesions involving major blood vessels Patients who have been treated with bevacizumab or other VEGFR inhibitor(s)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Open<br> | Drug: Axitinib (AG-013736)<br>* AG-013736 5mg twice daily [BID]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 3 or higher, serious adverse events, and adverse events resulted in discontinuation. | Up to 795 days of treatment plus 28-days follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax): Single Dose |  | Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Single Dose |  | Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose | 
| Area Under The Plasma Concentration-Time Curve From Time Zero to Time Infinity (AUCinf): Single Dose | AUCinf is obtained from AUC (0 - t) plus AUC (t - infinity). | Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose | 
| Terminal Phase Plasma Half-Life (t1/2): Single Dose | t1/2 is the time measured for the plasma concentration to decrease by one half. | Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose | 
| Maximum Observed Plasma Concentration (Cmax): Multiple Dose |  | Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax): Multiple Dose |  | Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose | 
| Area Under The Plasma Concentration-Time Curve Over Dosing Interval Tau (AUCtau): Multiple Dose | Dosing Interval was 12 hours in this study. | Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose | 
| Accumulation Ratio for Cmax (Rac Cmax) and Accumulation Ratio for AUCtau (Rac AUCtau): Multiple Dose | Rac Cmax is obtained from Cmax (Cycle 1, Day 15) divided by Cmax (Cycle 1, Day 1) Rac AUCtau is obtained from AUCtau (Cycle 1, Day 15) divided by AUCtau (Cycle 1, Day 1) | Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose | 
| Percent Change From Baseline in Soluble Vascular Endothelial Growth Factor Receptor 2 and 3 (s-VEGFR2 and s-VEGFR3), Vascular Endothelial Growth Factor (VEGF), Soluble Stem Cell Factor Receptor (s-KIT) | Percent change from baseline is obtained from (observed value minus baseline value) divided by baseline value multiplied by 100 in each parameter, i.e., VEGFR2, s-VEGFR3, s-KIT, and VEGF. | Prior to the initial dose (baseline), Day 1 of Cycle 2 and at the discontinuation | 
| The Numbers of Participants With Best Overall Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression of Disease (PD) According to the 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 (SLD) of the targeted lesions. CR and PR had to be documented on 2 occasions separated by at least 4 weeks. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify as PD being demonstrated during the first 8 weeks. PD was defined as at least a 20% increase in the SLD of target lesions compared to the smallest SLD since the study treatment started. | Up to 795 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, PK, Biomarker