Clinical trial NCT00557505: A Study Of PF-03732010 In Patients With Advanced Solid Tumors
Official title: A Phase 1 Pharmacokinetic And Pharmacodynamic Study Of PF-03732010 In Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle
measure: Recommended Phase-2 Dose (RP2D)
timeFrame: Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle
Secondary outcomes:
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-28 Day)]
timeFrame: 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
measure: Time to Reach Maximum Observed Serum Concentration (Tmax)
timeFrame: 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
measure: Minimum Observed Serum Trough Concentration (Cmin)
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-14 Day)]
timeFrame: 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
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: 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
measure: Clearance (CL)
timeFrame: 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
measure: Apparent Volume of Distribution (Vd)
timeFrame: 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
measure: Number of Participants With Objective Response of Complete Response or Partial Response
timeFrame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37
Other outcomes:
measure: Human Anti-Human Antibody (HAHA) Levels
timeFrame: 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
measure: Change From Baseline in Standardized Uptake Values (SUV) of 18F-fluoro-3'-Deoxy-3'-L-fluorothymidine Positron Emission Tomography (FLT-PET)
timeFrame: Baseline, cycle 3 and after 8 weeks
measure: Time to Disease Progression
timeFrame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37
measure: Change From Baseline in Circulating Tumor Cells (CTC) Concentration in Blood
timeFrame: 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
measure: Change From Baseline in Leucocyte Subtypes
timeFrame: Baseline, Day 1 cycle 1, Day 1 Cycle 2, Day 1 of every other cycle starting from cycle 3 up to EOT or withdrawal
measure: Change From Baseline in Cytokine Concentration
timeFrame: Pre-dose (baseline), 1, 6 and 24 hrs after start of infusion on Day 1 cycle 1
measure: Change From Baseline in Tumor Proteins Related to P-cadherin Signaling and/or Tumor Proliferation or Apoptosis by Immunohistochemistry (IHC)
timeFrame: Baseline and cycle 3
Locations:
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Parkville
country: Australia
facility: Pfizer Investigational Site
state: Victoria
city: Seoul
country: Korea, Republic of
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: