Clinical trial NCT00424632: Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors
Official title: A Phase 1, Open Label, Multi-Center, Accelerated Dose-Escalation, Pharmacokinetic And Pharmacodynamic Trial Of The Oral Single Agent Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors For Whom No Standard Therapy Is Available
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-01-19
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose and recommended phase 2 dose of PF-03814735 administered orally as single agent in patients with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Metastatic solid tumor resistant to standard therapy or for which no standard therapy is available
* Adequate bone marrow, liver and kidney function

Exclusion Criteria:

* Brain metastases that are symptomatic and/or require treatment with steroids and/or anticonvulsants, or brain metastases that have been treated within 3 months prior to study start
* Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident in the previous 6 months

Primary outcomes:
measure: Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Graded According to Common Terminology Criteria Adverse Events (CTCAE), Version 3
timeFrame: Day 1 up to Day 21 of first cycle
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Time for Maximum Observed Serum Concentration (Tmax)
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Area Under the Serum Concentration Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 24 Hours (AUCτ).
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Minimum Observed Serum Trough Concentration (Cmin)
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Observed Serum Accumulation Ratio (Rac)
timeFrame: Schedule B Day-5: pre-dose, 0.5, 1, 2, 4, 6, 10, 24, 32, 48, and 72 hours post-dose, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Terminal Half-life (t 1/2)
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Urine Pharmacokinetics
timeFrame: Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
measure: Summary of Tumor Metabolism Assessed by Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)
timeFrame: Baseline (Schedule A or Schedule B Day -7) and Schedule A Cycle 1/Day 3 or Day 4, Schedule B Cycle 1/Day 8 or 9
measure: Target Modulation by Phosphohistone H3 (pH3) Expression in Tumor Tissue (IHC)
timeFrame: Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10
measure: Number of Participants With Objective Tumor Response
timeFrame: Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles
measure: Time to Progression
timeFrame: Baseline, every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles
measure: Duration of Response
timeFrame: Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles
measure: Germ Line Polymorphism of Candidate Genes Targeted by PF-03814735
timeFrame: Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)
measure: Aurora Gene Somatic Mutations/Amplification and Pathway Genes in Tumor Tissue
timeFrame: Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Leuven
country: Belgium
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Schoffski P, Jones SF, Dumez H, Infante JR, Van Mieghem E, Fowst C, Gerletti P, Xu H, Jakubczak JL, English PA, Pierce KJ, Burris HA. Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. Eur J Cancer. 2011 Oct;47(15):2256-64. doi: 10.1016/j.ejca.2011.07.008. Epub 2011 Aug 16.