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A Study Of PF-03732010 In Patients With Advanced Solid Tumors

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: NCT00557505
Recruitment Status : Completed
First Posted : November 14, 2007
Results First Posted : March 26, 2012
Last Update Posted : March 26, 2012
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 12, 2007
First Posted Date  ICMJE November 14, 2007
Results First Submitted Date  ICMJE January 10, 2012
Results First Posted Date  ICMJE March 26, 2012
Last Update Posted Date March 26, 2012
Study Start Date  ICMJE December 2007
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2012)
  • Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle ]
  • Recommended Phase-2 Dose (RP2D) [ Time Frame: Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 12, 2007)
To determine the maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of PF-03732010 administered in patients with advanced solid tumors.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2012)
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-28 Day)] [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
    AUC (0-28 day)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-28 day).
  • Time to Reach Maximum Observed Serum Concentration (Tmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
  • Minimum Observed Serum Trough Concentration (Cmin) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
  • Maximum Observed Serum Concentration (Cmax) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-14 Day)] [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
    AUC (0-14)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-14 day).
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
  • Clearance (CL) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
  • Apparent Volume of Distribution (Vd) [ Time Frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 5, 10, 24 hrs after the start of infusion of first dose, Day 3, 5, 8, 11 of cycle 1; pre-dose and 1 hr after start of infusion in every other cycle starting from cycle 2 up to Week 4, 8 and 12 after last dose or withdrawal ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
  • Number of Participants With Objective Response of Complete Response or Partial Response [ Time Frame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37 ]
    Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with at least 30 percent decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2007)
  • To establish the safety profile of single-agent PF-03732010
  • To evaluate pharmacokinetics (PK) of PF-03732010
  • To evaluate the immunogenicity of PF-03732010
  • To assess effects of PF-03732010 on biomarkers, on an exploratory basis
  • To document any preliminary evidence of anti-tumor activity
Current Other Pre-specified Outcome Measures
 (submitted: February 21, 2012)
  • Human Anti-Human Antibody (HAHA) Levels [ Time Frame: Pre-dose on Day 1 of Cycle 2 and Day 1 of every other cycle up to Week 4, 8 and 12 after the last dose or withdrawal ]
    HAHA are indicators of immunogenicity to PF-03732010.
  • Change From Baseline in Standardized Uptake Values (SUV) of 18F-fluoro-3'-Deoxy-3'-L-fluorothymidine Positron Emission Tomography (FLT-PET) [ Time Frame: Baseline, cycle 3 and after 8 weeks ]
  • Time to Disease Progression [ Time Frame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37 ]
    Time in weeks from start of study treatment to first documentation of objective disease progression or death due to disease, whichever comes first.
  • Change From Baseline in Circulating Tumor Cells (CTC) Concentration in Blood [ Time Frame: Pre-dose (baseline), Day 8 cycle 1, Day 1 Cycle 2 and Day 1 of every other cycle starting from cycle 3 up to EOT or withdrawal ]
  • Change From Baseline in Leucocyte Subtypes [ Time Frame: Baseline, Day 1 cycle 1, Day 1 Cycle 2, Day 1 of every other cycle starting from cycle 3 up to EOT or withdrawal ]
  • Change From Baseline in Cytokine Concentration [ Time Frame: Pre-dose (baseline), 1, 6 and 24 hrs after start of infusion on Day 1 cycle 1 ]
  • Change From Baseline in Tumor Proteins Related to P-cadherin Signaling and/or Tumor Proliferation or Apoptosis by Immunohistochemistry (IHC) [ Time Frame: Baseline and cycle 3 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of PF-03732010 In Patients With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Pharmacokinetic And Pharmacodynamic Study Of PF-03732010 In Patients With Advanced Solid Tumors
Brief Summary P-cadherin may play a part in tumor growth; PF-03732010 is a new drug that inhibits P-cadherin. This study will test how well the drug is tolerated, and what effects there might be. Blood will also be taken to measure the amount of drug in blood.
Detailed Description Not Provided
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-03732010
IV infusion. Escalating dose levels, starting at 0.5 mg/kg to Maximum Tolerated Dose. Cycle length of 4 weeks for first cycle, and 2 weekly for subsequently cycles was originally explored, yet based on emerging PK data the Cycle 1 duration is 2 weeks and then weekly. Number of Cycles: Until Progression or unacceptable toxicity develops.
Study Arms  ICMJE Experimental: PF-03732010
Single Arm study
Intervention: Drug: PF-03732010
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 4, 2012)
43
Original Enrollment  ICMJE
 (submitted: November 12, 2007)
60
Actual Study Completion Date  ICMJE February 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Advanced solid tumors refractory to (or intolerant of) established therapy known to provide clinical benefit, or for which there is no standard therapy
  • Age >= 18 years of age
  • Adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥1500/uL, hemoglobin ≥ 9 g/dL, platelets > 100,000/uL
  • Adequate liver function as defined by: bilirubin < 1.5 x ULN, AST, ALT and ALP < 2.5 x ULN, or < 5 x ULN with documented liver and/or bone metastases
  • Serum creatinine < 1.5 x ULN
  • ECOG status 0-1
  • Availability of biopsy tumor tissue (or fine needle aspirate) for testing of P-cadherin expression
  • Tumor tissue (or fine needle aspirate) showing over-expression of P-cadherin
  • Must be able to give written informed consent
  • Be able to comply with scheduled study visits, treatment plans, laboratory tests and other procedures

Exclusion Criteria:

  • Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of study entry
  • Patients with carcinomatous meningitis or untreated brain metastases.
  • History of significant low platelet count, and/or bleeding disorders, requiring medical or surgical intervention
  • History of significant bleeding episodes within 6 months, unless the source of bleeding has been resected
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 Australia,   Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00557505
Other Study ID Numbers  ICMJE A9301001
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 February 2012

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