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Study of CP-751,871 in Combination With Docetaxel and Prednisone in Patients With Hormone Insensitive Prostate Cancer (HRPC)

Phase 2
Completed
Conditions
Prostatic Neoplasms
Interventions
Registration Number
NCT00313781
Lead Sponsor
Pfizer
Brief Summary

To test the efficacy of CP-751,871 combined with docetaxel and prednisone in the treatment of prostate cancer that is refractory to hormone therapy

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
204
Inclusion Criteria
  • Diagnosis of metastatic, progressive hormone refractory prostate cancer
  • Adequate bone marrow, liver and kidney function
Exclusion Criteria
  • Previous treatment with chemotherapy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ACP-751,871For patients treated with docetaxel and prednisone only, who progress during treatment, CP-751,871 will be added to the regimen to test reversibility of chemoresistance.
AdocetaxelFor patients treated with docetaxel and prednisone only, who progress during treatment, CP-751,871 will be added to the regimen to test reversibility of chemoresistance.
AprednisoneFor patients treated with docetaxel and prednisone only, who progress during treatment, CP-751,871 will be added to the regimen to test reversibility of chemoresistance.
Bdocetaxel-
Bprednisone-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Prostate Specific Antigen (PSA) Best ResponseBaseline, Day 1 and Day 15 of each cycle, end of treatment (up to 28 days post last dose) and follow-up (monthly, up to 150 days post last dose)

Percentage of participants with PSA best response of either PSA normalization (PN) or partial PSA response (PR) relative to the total number of participants evaluable for response. PN was defined as PSA =\< 0.2 nanogram/milliliter (ng/ml) on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. PP was defined as \>= 50% decrease in PSA from baseline on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose)

PFS was defined as the time from randomization to first event of disease progression. Disease progression events were defined as the following: PSA progression,objective disease progression as per RECIST, death, and discontinuation of treatment due to symptomatic deterioration. PSA progression was defined as the time-point of PSA progression on 2 successive evaluations taken 1 week apart after dosing in cycle 3.

Human Anti-human Antibody (HAHA) at the Last Follow-up VisitThe last follow-up visit (150 days post last dose)

Levels of HAHA in serum were detected at the last follow-up visit.

Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCsBaseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)

Blood samples were collected to enumerate the number of total IGF-1R positive CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive EpCAM and cytokeratin staining. A separate CellSave tube of cells was also collected and processed with cell surface staining of IGF-1R to enumerate surfaces of IGF-1R-positive CTCs.

Quality of Life Measured by the Functional Assessment of Cancer Treatment-Prostate (FACT-P)Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose)

The FACT-P was a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items were scored from 0 (not at all) to 4 (very much). The total FACT-P score ranged from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represented the best outcome.

Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)
Maximum Observed Plasma Concentration (Cmax) for CP-751,871Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)
Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1)Baseline (Day 1 of Cycle 1)

Levels of HAHA in serum were detected at baseline.

Population PK Parameters of CP-751,871Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)

Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for CP-751,871 and to determine inter-individual and residual variability in population clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured CP-751,871 concentrations

Total Number of Circulation Tumor Cells (CTCs)Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)

Blood samples were collected and processed to enumerate the number of total CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive epithelial cell adhesion molecule (EpCAM) and cytokeratin staining.

Pain Measured by the Modified Brief Pain Inventory-Short Form (mBPI-sf Modified Pfizer)Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose)

The mBPI-sf was a self administered questionnaire developed to assess pain severity and pain interference with functional activities during a 24-hour period prior to evaluation. For the worst pain item of the mBPI-sf scale (11 point Likert scale; range: 0 \[no pain\] to 10 \[pain as bad as you can imagine\]), participants were asked to rate their pain by marking an "X" in one of the 10 boxes that best described their pain at its worst in the last 24 hours post surgery and at least 12 hours after discontinuation of the peripheral nerve block or neuraxial block.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for CP-751,871Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)

Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration.

Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-tau) for CP-751,871Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose)

Trial Locations

Locations (1)

Pfizer Investigational Site

🇬🇧

Guildford, United Kingdom

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