Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of PF-04217903 in Patients With Advanced Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00706355
Recruitment Status : Terminated (See termination reason in detailed description.)
First Posted : June 27, 2008
Results First Posted : May 31, 2012
Last Update Posted : June 25, 2012
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: PF-04217903 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of PF-4217903 in Patients With Advanced Cancer
Study Start Date : August 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Arm Intervention/treatment
Experimental: 1 Drug: PF-04217903
Escalating doses of PF-04217903 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg BID to 1000 mg BID. A cycle is considered to be 21 days




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 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.

  2. Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline up to 21 days after the start of each increased treatment dose ]
  3. Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: 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 :
  1. Maximum Observed Plasma Concentration (Cmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 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 ]
  2. Minimum Observed Plasma Trough Concentration (Cmin) for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 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.

  3. Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1 ]
  4. Pre-dose Plasma Concentration (Ctrough) for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 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.

  5. 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) [ Time Frame: 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).

  6. Area Under the Curve From Time Zero to End of Dosing Interval [AUC(0-tau)] for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 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.

  7. Accumulation Ratio (Rac) for PF-04217903 and PF-04217903 Metabolite (PF-04328029) [ Time Frame: 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.

  8. Metabolite to Parent Ratio Area Under the Curve From Time Zero to End of Dosing Interval (MRAUCtau) [ Time Frame: 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).

  9. Apparent Oral Clearance (CL/F) for PF-04217903 [ Time Frame: 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.

  10. 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 [ Time Frame: 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).

  11. Percentage of Participants With Objective Response (OR) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00706355


Locations
Layout table for location information
United States, Colorado
Pfizer Investigational Site
Aurora, Colorado, United States, 80045
United States, Illinois
Pfizer Investigational Site
Chicago, Illinois, United States, 60637
United States, Massachusetts
Pfizer Investigational Site
Boston, Massachusetts, United States, 02114
Pfizer Investigational Site
Boston, Massachusetts, United States, 02115
Pfizer Investigational Site
Boston, Massachusetts, United States, 02215
United States, Michigan
Pfizer Investigational Site
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00706355    
Other Study ID Numbers: B0331002
First Posted: June 27, 2008    Key Record Dates
Results First Posted: May 31, 2012
Last Update Posted: June 25, 2012
Last Verified: June 2012