Clinical trial NCT00706355: A Study of PF-04217903 in Patients With Advanced Cancer
Official title: Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of PF-4217903 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: PF-04217903 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-04217903 is a new member in a class of drugs called c-Met/hepatocyte growth factor receptor tyrosine kinase inhibitors. This research study is the first time PF-04217903 will be given to patients. PF-04217903 is taken by mouth daily.

Detailed description: The study was prematurely discontinued due to a strategic development decision by Pfizer on 10FEB2012. The decision to terminate was not based on any safety concerns.

Eligibility criteria: Inclusion Criteria:

* Advanced solid tumors, histologically proven at diagnosis which is refractory to standard of care or for whom no standard of care therapy is available
* Adequate blood cell counts, normal kidney function, and performance status of 0 or 1

Exclusion Criteria:

* Major surgery, radiation therapy or anti-cancer therapy within 2 weeks of starting study treatment
* Prior stem cell transplant
* Active or unstable cardiac disease or heart attack within 12 months of starting study treatment

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Baseline up to 21 days after the start of each increased treatment dose
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Baseline up to 21 days after the start of each increased treatment dose
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Baseline up to 21 days after the start of each increased treatment dose
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hours (hrs) (just prior to evening dosing) post dose on Cycle (C) 1 Day (D) 1 and C2 D1
measure: Minimum Observed Plasma Trough Concentration (Cmin) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
measure: Pre-dose Plasma Concentration (Ctrough) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
measure: Area Under the Plasma Concentration Time-curve From Zero to the Last Measured Concentration [AUC(0-last)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
measure: Area Under the Curve From Time Zero to End of Dosing Interval [AUC(0-tau)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
measure: Accumulation Ratio (Rac) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1
measure: Metabolite to Parent Ratio Area Under the Curve From Time Zero to End of Dosing Interval (MRAUCtau)
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
measure: Apparent Oral Clearance (CL/F) for PF-04217903
timeFrame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1
measure: Change From Baseline in Tumor Proliferation Using F-Fluoro-3'-Deoxy-3'-L-Fluorothymidine Positron Emission Tomography (FLT-PET) Imaging at Day 1 of Cycle 2
timeFrame: Cycle 2 Day 1
measure: Percentage of Participants With Objective Response (OR)
timeFrame: Baseline until disease progression up to C2 D1
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Diamond JR, Salgia R, Varella-Garcia M, Kanteti R, LoRusso PM, Clark JW, Xu LG, Wilner K, Eckhardt SG, Ching KA, Lira ME, Schoenmakers EF, Christensen JG, Camidge DR. Initial clinical sensitivity and acquired resistance to MET inhibition in MET-mutated papillary renal cell carcinoma. J Clin Oncol. 2013 Jun 1;31(16):e254-8. doi: 10.1200/JCO.2012.46.4289. Epub 2013 Apr 22. No abstract available.