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

• Progression Free Survival (PFS) [ Time Frame: Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose) ] [ Designated as safety issue: No ]
  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 Baseline (Day 1 of Cycle 1) [ Time Frame: Baseline (Day 1 of Cycle 1) ] [ Designated as safety issue: No ]
  Levels of HAHA in serum were detected at baseline.
• Human Anti-human Antibody (HAHA) at the Last Follow-up Visit [ Time Frame: The last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]
  Levels of HAHA in serum were detected at the last follow-up visit.
• Population PK Parameters of CP-751,871 [ Time Frame: Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]
  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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
  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.
• Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs [ Time Frame: 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) ] [ Designated as safety issue: No ]
  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) [ Time Frame: Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) ] [ Designated as safety issue: No ]
  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.
• Pain Measured by the Modified Brief Pain Inventory‑Short Form (mBPI‑sf Modified Pfizer) [ Time Frame: Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) ] [ Designated as safety issue: No ]
  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-751,871 [ Time Frame: Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]
  Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration.
• Maximum Observed Plasma Concentration (Cmax) for CP-751,871 [ Time Frame: Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]
• Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 [ Time Frame: Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]
• Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-tau) for CP-751,871 [ Time Frame: Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) ] [ Designated as safety issue: No ]

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

• Drug: CP-751,871
  CP-750,871 is administered intravenously at a dose of 20 mg/kg on day 1 of each 21-day cycle (for patient convenience and logistical management, the dose of CP-751,871 may be deferred up to 7 days).
• Drug: docetaxel
  Docetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.
• Drug: prednisone
  Prednisone is administered at a dose of 5 mg twice daily.

• Experimental: A
  For 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.
  Interventions:

  • Drug: CP-751,871
  • Drug: docetaxel
  • Drug: prednisone
• Active Comparator: B
  Interventions:

  • Drug: docetaxel
  • Drug: prednisone

Inclusion Criteria:

• Diagnosis of metastatic, progressive hormone refractory prostate cancer
• Adequate bone marrow, liver and kidney function

Exclusion Criteria:

• Previous treatment with chemotherapy