A Study In Patients With Advanced Solid Tumor

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

This study designed to evaluate the pharmacokinetics and safety of AG-013736 at single doses and multiple doses

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Axitinib (AG-013736)

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hyogo-ken
    • Kobe-shi, Hyogo-ken, Japan
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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: Axitinib	Drug: Axitinib (AG-013736); 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.

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

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: July 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: July 30, 2008
• First Submitted That Met QC Criteria: July 30, 2008
• First Posted (Estimate): August 1, 2008

Study Record Updates

• Last Update Posted (Estimate): May 23, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; solid tumor; Axitinib
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: A4061044