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

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00557505
• Other study ID #: A9301001
• Status: Completed
• Phase: Phase 1
• First received: November 12, 2007
• Last updated: February 21, 2012
• Start date: December 2007
• Est. completion date: February 2011

Study information

• Verified date: February 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Australia	Pfizer Investigational Site	Parkville	Victoria
Korea, Republic of	Pfizer Investigational Site	Seoul
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)		Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle	Yes
Primary	Recommended Phase-2 Dose (RP2D)		Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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