An Efficacy and Safety Study of Intetumumab (CNTO 95) in Participants With Metastatic Hormone Refractory Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the effects of intetumumab when given in combination with docetaxel and prednisone to participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body until it kills).

Detailed Description
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This is a multicenter (when more than one hospital or medical school team work on a medical research study), randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives) study of intetumumab in combination with docetaxel and prednisone for the first-line treatment of participants with metastatic hormone-refractory prostate cancer. There will be 2 study groups. One group will receive intetumumab in combination with docetaxel and prednisone (study treatment) and the other group will receive placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) matching to intetumumab in combination with docetaxel and prednisone (control treatment). The duration of treatment will be 6 months. Participants who respond to treatment with stable disease or better will receive extended treatment until disease progression (disease worsening) or for an additional 6 months, whichever occurs first. Treatment can be further continued with the sponsor's discretion after receiving 6 months of extended treatment, if participant response to the treatment (with stable disease, partial response, or complete response). Participants who have confirmed progressive disease while receiving study treatment may have their treatment unblinded (participants will know the name of drug which was given to them), if they wish to be considered for alternative treatment. Participants who were receiving the control treatment will be considered to have completed the study treatment, and will have the option to receive alternative treatment. Alternative treatment will either be intetumumab along with docetaxel and prednisone or intetumumab alone. Participants' safety will be monitored throughout the study.

Official Title
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A Randomized, Double-blind, Multicenter, Phase 2 Study of a Human Monoclonal Antibody to Human av Integrins (CNTO 95) in Combination With Docetaxel for the First-Line Treatment of Subjects With Metastatic Hormone Refractory Prostate Cancer

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Prednisone
* Biological: Intetumumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Confirmed cancer of the prostate Evidence of metastatic disease Have a life expectancy greater than 12 weeks Have at least 4 weeks from previous major surgery to date of first study agent given Have progressive hormone-refractory disease after orchiectomy or gonadotropin-releasing hormone analog and/or antiandrogen treatment within 6 months prior to the first study agent administration Exclusion Criteria Have known Central Nervous System metastases (cancerous tumors that have spread to the brain from somewhere else in the body) Had prior systemic non-hormonal therapy for hormone refractory prostate cancer Have known Human Immunodeficiency Virus (HIV, a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) seropositivity or known hepatitis B or C infection Have planned major surgery during the study Have taken any over-the-counter (medicine that can be bought without a prescription) or herbal treatment for prostate cancer within 4 weeks prior to the first study treatment administration

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Docetaxel + Prednisone + Placebo<br>Matching placebo as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. | Drug: Docetaxel<br>* Docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks.<br>Drug: Prednisone<br>* Prednisone 5 mg orally twice daily.<br>Drug: Placebo<br>* Placebo matching to intetumumab, as intravenous infusion every week for initial 6 weeks, then every 3 weeks.<br>|
| Experimental: Docetaxel + Prednisone + Intetumumab<br>Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. | Drug: Docetaxel<br>* Docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks.<br>Drug: Prednisone<br>* Prednisone 5 mg orally twice daily.<br>Biological: Intetumumab<br>* Intetumumab 10 mg/kg as intravenous infusion every week for initial 6 weeks, then every 3 weeks.<br>* Other names: CNTO 95;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. | Baseline up to 6 months after last dose of study treatment, assessed up to 551 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Overall Response (OR) | Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. | Baseline up to 6 months after last dose of study treatment, assessed up to 551 days | 
| Number of Participants With Prostate Specific Antigen (PSA) Response | The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later). | Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days | 
| Overall Survival | Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date. | Baseline until death (up to 887 days) | 
| Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. | Baseline, Week 6, 7, 10 and 13 | 
| Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. | Baseline, Week 6, 7, 10 and 13 | 
| Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration | Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. | Baseline, Week 6, 7, 10 and 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatic neoplasms, CNTO 95, Intetumumab, Docetaxel, Prednisone