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

A Phase 1 Pharmacokinetic And Pharmacodynamic Study Of PF-03732010 In Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: PF-03732010

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Pfizer Investigational Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Pfizer Investigational Site
• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-03732010; Single Arm study	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD)	Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle
Recommended Phase-2 Dose (RP2D)	Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-28 Day)]	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).	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
Time to Reach Maximum Observed Serum Concentration (Tmax)		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)		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)		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)]	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).	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 (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).	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 (CL)	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.	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
Apparent Volume of Distribution (Vd)	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.	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
Number of Participants With Objective Response of Complete Response or Partial Response	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.	Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Human Anti-Human Antibody (HAHA) Levels	HAHA are indicators of immunogenicity to PF-03732010.	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
Change From Baseline in Standardized Uptake Values (SUV) of 18F-fluoro-3'-Deoxy-3'-L-fluorothymidine Positron Emission Tomography (FLT-PET)		Baseline, cycle 3 and after 8 weeks
Time to Disease Progression	Time in weeks from start of study treatment to first documentation of objective disease progression or death due to disease, whichever comes first.	Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37
Change From Baseline in Circulating Tumor Cells (CTC) Concentration in Blood		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		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		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)		Baseline and cycle 3

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: November 12, 2007
• First Submitted That Met QC Criteria: November 12, 2007
• First Posted (Estimate): November 14, 2007

Study Record Updates

• Last Update Posted (Estimate): March 26, 2012
• Last Update Submitted That Met QC Criteria: February 21, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: A9301001