A Study In Patients With Advanced Solid Tumor

Study Overview
=================
Brief Summary
-----------------
This study designed to evaluate the pharmacokinetics and safety of AG-013736 at single doses and multiple doses

Official Title
-----------------
A Phase 1 Study In Patients With Advanced Solid Tumor To Evaluate The Pharmacokinetics And Safety Of AG-013736 At Single Doses Of 5 mg, 7 mg And 10 mg, And At Multiple Doses

Conditions
-----------------
Neoplasms

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients histologically or cytologically diagnosed with advanced solid tumors Patients for whom standard therapies have not been effective, or for whom there are no suitable therapies Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2 Patients with no uncontrolled hypertension Exclusion Criteria: Patients who have central lung lesions involving major blood vessels Patients who require anticoagulant therapy. Patients with active epilepsy seizure or symptoms, with brain metastases requiring treatment, with spinal cord compression and with carcinomatous meningitis.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Axitinib<br> | Drug: Axitinib (AG-013736)<br>* Three single dose level of AG-013736 (5 mg, 7 mg and 10 mg) will be given for all patient. After single dosing at each dose level, multiple doses of 5 mg twice a day (BID) will be started.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose: Maximum Observed Plasma Concentration (Cmax) |  | Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time Infinity (AUCinf) | AUCinf is obtained from AUC (0 - t) plus AUC (t - infinity). | Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose | 
| Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose | 
| Single Dose: Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Predose, 0.5, 1, 2, 4, 6, 8, 10, 24, and 32-hour postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Dose: Maximum Observed Plasma Concentration (Cmax) | Cmax at multiple dosing | Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose | 
| Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | The dosing interval was 12 hours in this study. | Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose | 
| Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) | Tmax at multiple dosing | Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose | 
| Multiple Dose: Accumulation Ratio for Cmax (Rac Cmax) and Accumulation Ratio for AUCtau (Rac AUCtau) | 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) | Cycle 1 Day 15 predose in the morning, and 0.5, 1, 2, 4, 8 and 12 hour postdose | 
| Percent Change From Baseline in Soluble Vascular Endothelial Growth Factor Receptor 1, 2, and 3 (s-VEGFR1, 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., s-VEGFR1, VEGFR2, s-VEGFR3, s-KIT, and VEGF | Prior to the initial dose (baseline) and Day 1 of Cycle 2 | 
| Number 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 470 days | 
| Number of Participants With Adverse Events | Number of participants with any adverse events, adverse events graded as Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade 3 or higher , serious adverse events, and adverse events resulted in discontinuation. | Up to 470 days of treatment plus 28-days follow-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
solid tumor, Axitinib, Pharmacokinetics, Phase 1