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

Study Overview
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Brief Summary
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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

Official Title
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A Phase 2, Randomized, Non-Comparative, Two-Arm Open Label, Multiple-Center Study Of CP-751,871 In Combination With Docetaxel/Prednisone In Chemotherapy- Naive (Arm A) And Docetaxel/Prednisone Refractory (Arm B) Patients With Hormone Insensitive Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: CP-751,871
* Drug: docetaxel
* Drug: prednisone
* Drug: docetaxel
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of metastatic, progressive hormone refractory prostate cancer Adequate bone marrow, liver and kidney function Exclusion Criteria: Previous treatment with chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>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. | Drug: CP-751,871<br>* 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).<br>Drug: docetaxel<br>* Docetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.<br>Drug: prednisone<br>* Prednisone is administered at a dose of 5 mg twice daily.<br>|
| Active Comparator: B<br> | Drug: docetaxel<br>* Docetaxel is administered IV on day 1 of each 21-day cycle, at a dose of 75 mg/m2.<br>Drug: prednisone<br>* Prednisone is administered at a dose of 5 mg twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Prostate Specific Antigen (PSA) Best Response | 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. | Baseline, 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | 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. | Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose) | 
| Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1) | Levels of HAHA in serum were detected at baseline. | Baseline (Day 1 of Cycle 1) | 
| Human Anti-human Antibody (HAHA) at the Last Follow-up Visit | Levels of HAHA in serum were detected at the last follow-up visit. | The last follow-up visit (150 days post last dose) | 
| Population PK Parameters of CP-751,871 | 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 | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) | 
| Total Number of Circulation Tumor Cells (CTCs) | 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. | 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) | 
| Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs | 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. | 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) | 
| Quality of Life Measured by the Functional Assessment of Cancer Treatment-Prostate (FACT-P) | 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. | Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) | 
| Pain Measured by the Modified Brief Pain Inventory-Short Form (mBPI-sf Modified Pfizer) | 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. | Baseline, Cycle 1 to Cycle 10 before drug administration and end of treatment (up to 28 days post last dose) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) for CP-751,871 | Area under the plasma concentration versus time curve from time zero to time of last quantifiable concentration. | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) | 
| Maximum Observed Plasma Concentration (Cmax) for CP-751,871 |  | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) | 
| Minimum Observed Plasma Trough Concentration (Cmin) for CP-751,871 |  | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUC0-tau) for CP-751,871 |  | Days 1, 8 and 15 of each cycle and last follow-up visit (150 days post last dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized, non-comparative, efficacy