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

• ClinicalTrials.gov Identifier: NCT00447005
• Recruitment Status: Completed
• First Posted: March 13, 2007
• Results First Posted: March 26, 2012
• Last Update Posted: May 23, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 12, 2007
• First Posted Date: March 13, 2007
• Results First Submitted Date: February 25, 2012
• Results First Posted Date: March 26, 2012
• Last Update Posted Date: May 23, 2012
• Study Start Date: February 2007
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 17, 2012)

Number of Participants With Adverse Events [ Time Frame: Up to 795 days of treatment plus 28-days follow-up ]

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.

• Original Primary Outcome Measures (submitted: March 12, 2007): The incidence of all adverse events by type and grade, Abnormal laboratory changes(every 2 weeks)

Current Secondary Outcome Measures (submitted: February 25, 2012)

• Maximum Observed Plasma Concentration (Cmax): Single Dose [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose ]
  AUCinf is obtained from AUC (0 - t) plus AUC (t - infinity).
• Terminal Phase Plasma Half-Life (t1/2): Single Dose [ Time Frame: Single dose: predose, 0.5, 1, 2, 4, 6, 8, 12, 24, and 32 hours postdose ]
  t1/2 is the time measured for the plasma concentration to decrease by one half.
• Maximum Observed Plasma Concentration (Cmax): Multiple Dose [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose ]
  Dosing Interval was 12 hours in this study.
• Accumulation Ratio for Cmax (Rac Cmax) and Accumulation Ratio for AUCtau (Rac AUCtau): Multiple Dose [ Time Frame: Multiple dose Cycle 1 Day 1 and 15: predose, 0.5, 1, 2, 4, 8 and 12 hours postdose ]
  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)
• 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) [ Time Frame: Prior to the initial dose (baseline), Day 1 of Cycle 2 and at the discontinuation ]
  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.
• 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) [ Time Frame: Up to 795 days ]
  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.

• Original Secondary Outcome Measures (submitted: March 12, 2007): Pharmacokinetics (at single dosing, 1st ,15th and 29th day of multiple dosing following single dosing) Pharmacodynamic indices (4 times every 4 weeks and end of treatment) Anti-tumor activity (every 8 weeks until end of treatment)
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Of AG-013736 (Axitinib) In Patients With Advanced Solid Tumors
• Official Title: A Phase 1 Study Of AG-013736 (Axitinib) In Japanese Patients With Advanced Solid Tumors
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma

Intervention

Drug: Axitinib (AG-013736)

AG-013736 5mg twice daily [BID]

Study Arms

Experimental: Open

Intervention: Drug: Axitinib (AG-013736)

• Publications *: Mukohara T, Nakajima H, Mukai H, Nagai S, Itoh K, Umeyama Y, Hashimoto J, Minami H. Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients. Cancer Sci. 2010 Apr;101(4):963-8. doi: 10.1111/j.1349-7006.2009.01465.x. Epub 2009 Dec 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2007): 12
• Original Enrollment: Same as current
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00447005
• Other Study ID Numbers: A4061022
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Not Provided
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2012