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Completed

NCT Number: NCT00557505

A 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.

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Key information

Conditions

Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site, Parkville, Victoria, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PF-03732010

Drug

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.

Primary outcomes

  1. Maximum Tolerated Dose (MTD)

    Time frame: Baseline up to end of treatment (EOT) or withdrawal assessed up to Day 7 of last cycle

  2. Recommended Phase-2 Dose (RP2D)

    Time frame: Baseline up to EOT or withdrawal assessed up to Day 7 of last cycle

Secondary outcomes

  1. 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

    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).

  2. 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

  3. 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

  4. 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

  5. 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

    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).

  6. 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

    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

  7. 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

    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.

  8. 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

    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.

  9. 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

    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.

Other outcomes

  1. Human Anti-Human Antibody (HAHA) Levels

    Time frame: 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

    HAHA are indicators of immunogenicity to PF-03732010.

  2. Change From Baseline in Standardized Uptake Values (SUV) of 18F-fluoro-3'-Deoxy-3'-L-fluorothymidine Positron Emission Tomography (FLT-PET)

    Time frame: Baseline, cycle 3 and after 8 weeks

  3. Time to Disease Progression

    Time frame: Baseline to disease progression or 4 weeks after the first dose and then every 6 weeks up to Week 37

    Time in weeks from start of study treatment to first documentation of objective disease progression or death due to disease, whichever comes first.

  4. Change From Baseline in Circulating Tumor Cells (CTC) Concentration in Blood

    Time frame: 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

  5. Change From Baseline in Leucocyte Subtypes

    Time frame: Baseline, Day 1 cycle 1, Day 1 Cycle 2, Day 1 of every other cycle starting from cycle 3 up to EOT or withdrawal

  6. Change From Baseline in Cytokine Concentration

    Time frame: Pre-dose (baseline), 1, 6 and 24 hrs after start of infusion on Day 1 cycle 1

  7. Change From Baseline in Tumor Proteins Related to P-cadherin Signaling and/or Tumor Proliferation or Apoptosis by Immunohistochemistry (IHC)

    Time frame: Baseline and cycle 3

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

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

Important dates

Study start
2007
Primary completion
2011
Study completion
2011
First posted
Nov 14, 2007
Registry last updated
Mar 26, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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