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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
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.
Pfizer Investigational Site
Philadelphia, Pennsylvania, United States
Pfizer Investigational Site
Parkville, Victoria, Australia
Pfizer Investigational Site
Seoul, South Korea
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
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).
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
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
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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).
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 (AUClast)
Area under the plasma concentration time-curve from zero to the last measured 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
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.
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
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.
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
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.
Time frame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37