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

Phase 1
Completed
Conditions
Advanced Solid Tumors
Interventions
Registration Number
NCT01469052
Lead Sponsor
Pfizer
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
36
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort 1AG-013736-
Cohort 2AG-013736-
Cohort 3AG-013736-
Cohort 4AG-013736-
Cohort 5AG-013736-
Cohort 6AG-013736-
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated Dose (MTD)Baseline up to Day 28

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
NameTimeMethod
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)
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)
Area Under the Curve From Time Zero to 12 Hours [AUC (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)

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)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)

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)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)

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 FastingPre-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)
Time to Reach Maximum Observed Plasma Concentration (Tmax) in Fed State Versus Overnight FastingPre-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)
Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] in Fed State Versus Overnight FastingPre-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)

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 FastingPre-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)

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 FastingPre-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)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Madison, Wisconsin, United States

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