First In Human, Phase 1 Study of AG013736 In Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01469052
First received: November 2, 2011
Last updated: February 25, 2012
Last verified: February 2012
  Purpose

The purpose of the study was to characterize the safety of investigational agent AG-013736, in patients with solid tumors in this First In Human trial.


Condition Intervention Phase
Advanced Solid Tumors
Drug: AG-013736
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I, Open-Label, Multicenter, Dose-Escalation Study Of The Tyrosine Kinase Inhibitor Of VEGFR-2, AG013736, In Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to Day 28 ] [ Designated as safety issue: Yes ]
    MTD is defined as the dose level at which "no more than 1 of 6 participants experience dose-limiting toxicity (DLT) following de-escalation from the maximum administered dose (MAD)." DLT includes grade (Gr) 2 or greater gastrointestinal toxicities, Gr 3 anemia, nonhematological toxicities (excluding nausea, vomiting, and diarrhea) or Gr 4 neutropenia, thrombocytopenia and inability to resume axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hours (hrs) post-dose on Day (D) 1 and 15 of Cycle (C) 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)] [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) ] [ Designated as safety issue: No ]
    AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12).

  • Apparent Oral Clearance (CL/F) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Plasma Decay Half-Life (t1/2) [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 1 and 15 of Cycle 1 and Day 29 (Day 1 of Cycle 2); pre-dose on Day 43 (Day 15 of Cycle 2) and Day 57 (Day 1 of Cycle 3) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

  • Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) ] [ Designated as safety issue: No ]
    AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

  • Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) ] [ Designated as safety issue: No ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  • Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting [ Time Frame: Pre-dose, 0.5, 1, 2, 4, 8, and 12 hrs post-dose on Day 29 (Day 1 of Cycle 2) and Day 30 (Day 2 of Cycle 2) ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.


Enrollment: 36
Study Start Date: November 2002
Study Completion Date: August 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Drug: AG-013736
Axitinib continuous oral dosing (10 mg once a day, 10 mg twice a day, 20 mg twice a day or 30 mg twice day) in the fed state
Experimental: Cohort 2 Drug: AG-013736
Axitinib continuous oral dosing (20 mg twice a day) in the fed state
Experimental: Cohort 3 Drug: AG-013736
Axitinib continuous oral dosing (5 mg twice a day) in the fed state
Experimental: Cohort 4 Drug: AG-013736
Axitinib continuous oral dosing (15 mg once a day) in the fed state
Experimental: Cohort 5 Drug: AG-013736
Axitinib continuous oral dosing (5 mg twice a day) in the fasted state
Experimental: Cohort 6 Drug: AG-013736
Axitinib continuous oral dosing (2 mg twice a day on the first day of dosing, followed by 5 mg twice a day) in the fasted state

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with cytologically or histologically confirmed solid tumor(s) and with at least one measurable disease site
  • Patients with adequate bone marrow, liver and kidney function
  • Patients with life expectancy of at least 12 weeks

Exclusion Criteria:

  • Patients who have received chemotherapy, immunotherapy, radiotherapy or any investigational agent within 4 weeks of study entry
  • Patients with have had a major surgical procedure within 4 weeks of study entry
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01469052

Locations
United States, California
Pfizer Investigational Site
San Francisco, California, United States, 94115
United States, Texas
Pfizer Investigational Site
Houston, Texas, United States, 77030
United States, Wisconsin
Pfizer Investigational Site
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01469052     History of Changes
Other Study ID Numbers: AG013736-001, A4060010
Study First Received: November 2, 2011
Results First Received: February 25, 2012
Last Updated: February 25, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014