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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01469052
• Other study ID #: AG013736-001
• Secondary ID: A4060010
• Status: Completed
• Phase: Phase 1
• First received: November 2, 2011
• Last updated: February 25, 2012
• Start date: November 2002
• Est. completion date: August 2004

Study information

• Verified date: February 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2004
• Est. primary completion date: July 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors

Intervention

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
• AG-013736
Axitinib continuous oral dosing (20 mg twice a day) in the fed state
• AG-013736
Axitinib continuous oral dosing (5 mg twice a day) in the fed state
• AG-013736
Axitinib continuous oral dosing (15 mg once a day) in the fed state
• AG-013736
Axitinib continuous oral dosing (5 mg twice a day) in the fasted state
• 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

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Madison	Wisconsin
United States	Pfizer Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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.	Baseline up to Day 28	Yes
Secondary	Maximum Observed Plasma Concentration (Cmax)		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)	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		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)	No
Secondary	Area Under the Curve From Time Zero to 12 Hours [AUC (0-12)]	AUC (0-12)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-12).	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)	No
Secondary	Apparent Oral Clearance (CL/F)	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.	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)	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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)	No
Secondary	Maximum Observed Plasma Concentration (Cmax) in Fed State Versus Overnight Fasting		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)	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight Fasting		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)	No
Secondary	Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight Fasting	AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).	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)	No
Secondary	Apparent Oral Clearance (CL/F) in Fed State Versus Overnight Fasting	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.	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)	No
Secondary	Plasma Decay Half-Life (t1/2) in Fed State Versus Overnight Fasting	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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)	No

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