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Trial record 1 of 1 for:    NCT00706355
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A Study of PF-04217903 in Patients With Advanced Cancer

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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

Tracking Information
First Submitted Date  ICMJE June 25, 2008
First Posted Date  ICMJE June 27, 2008
Results First Submitted Date  ICMJE April 26, 2012
Results First Posted Date  ICMJE May 31, 2012
Last Update Posted Date June 25, 2012
Study Start Date  ICMJE August 2008
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2012)
  • 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.
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Baseline up to 21 days after the start of each increased treatment dose ]
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 25, 2008)
  • To test the safety of PF-04217903 when taken by people who have cancer [ Time Frame: 2 years ]
  • To assess how the body handles blood concentrations of PF-04217903 [ Time Frame: 2 years ]
  • To find the dose of PF-04217903 that should be used in future clinical trials [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2012)
  • 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 ]
  • 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.
  • 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 ]
  • 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.
  • 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).
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PF-04217903 in Patients With Advanced Cancer
Official Title  ICMJE Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of PF-4217903 in Patients With Advanced Cancer
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: 1
Intervention: Drug: PF-04217903
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 29, 2011)
16
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2008)
40
Actual Study Completion Date  ICMJE June 2011
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00706355
Other Study ID Numbers  ICMJE B0331002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP