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

Purpose

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.

Condition	Intervention	Phase
Neoplasms	Drug: PF-03732010	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Pharmacokinetic And Pharmacodynamic Study Of PF-03732010 In Patients With Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle ] [ Designated as safety issue: Yes ]
Recommended Phase-2 Dose (RP2D) [ Time Frame: Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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.

Enrollment:	43
Study Start Date:	December 2007
Study Completion Date:	February 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557505

Locations

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

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00557505 History of Changes
Other Study ID Numbers:	A9301001
Study First Received:	November 12, 2007
Results First Received:	January 10, 2012
Last Updated:	February 21, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on October 17, 2012