A Study of PF-04217903 in Patients With Advanced Cancer

Phase 1

Terminated

• Conditions: Neoplasms
• Interventions: Drug: PF-04217903

• Registration Number: NCT00706355
• Lead Sponsor: Pfizer

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.

Study Timeline

• Study First Submitted: 2008-06-25
• Study First Submitted QC: 2008-06-25
• Study First Posted: 2008-06-27
• Study Start: 2008-08
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Results First Submitted: 2012-04-26
• Results First Submitted QC: 2012-04-26
• Results First Posted: 2012-05-31
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-15
• Last Update Posted: 2012-06-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 16

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	PF-04217903	-

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	Baseline up to 21 days after the start of each increased treatment dose	MTD: dose level at which 1 of 6 participants experienced dose-limiting toxicity (DLT) after 21 days of treatment (Cycle 1). DLT: grade (Gr) 2 elevated creatinine, acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable),Gr \>=3 non-hematological non-disease-related (NDR) toxicities (except alopecia,Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>=7 days, febrile neutropenia, neutropenic infection, inability to deliver 80 percent of planned dose during Cycle 1 due to NDR toxicities.
Recommended Phase 2 Dose (RP2D)	Baseline up to 21 days after the start of each increased treatment dose
Number of Participants With Dose-Limiting Toxicities (DLTs)	Baseline up to 21 days after the start of each increased treatment dose	DLT includes Gr 2 elevated creatinine and acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable), Gr \>= 3 non-hematological non-disease-related (NDR) toxicities (except alopecia, Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>= 7 days, febrile neutropenia, neutropenic infection, inability to deliver at least 80 percent of planned dose during Cycle 1 due to NDR adverse events.

Secondary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	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
Minimum Observed Plasma Trough Concentration (Cmin) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1	Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1
Pre-dose Plasma Concentration (Ctrough) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1	Participants did not receive 200 mg twice a day dose of study treatment for this specific 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)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Area Under the Curve From Time Zero to End of Dosing Interval [AUC(0-tau)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1	Area under the concentration-time profile from time zero to time tau (dosing interval), where tau is equal to 12 hours.
Accumulation Ratio (Rac) for PF-04217903 and PF-04217903 Metabolite (PF-04328029)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1	Rac is obtained from AUCtau (Cycle 2 Day 1) divided by AUCtau (Cycle 1 Day 1). Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.
Metabolite to Parent Ratio Area Under the Curve From Time Zero to End of Dosing Interval (MRAUCtau)	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1	Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to end of dosing interval (MRAUCtau).
Apparent Oral Clearance (CL/F) for PF-04217903	0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1	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. Participants did not receive 200 mg twice a day dose of study treatment for this specific 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	Cycle 2 Day 1	F-fluoro-3'-deoxy-3'-L-fluorothymidine positron emission tomography (FLT-PET) imaging was used to assess the tumor proliferation in RP2D cohorts. Results of the FLT-PET were scored according to the methods developed by the American College of Radiology Imaging Network (ACRIN).
Percentage of Participants With Objective Response (OR)	Baseline until disease progression up to C2 D1	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 Detroit, Michigan, United States