Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

Study Overview
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Brief Summary
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Rationale: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known if vaccine therapy is effective for prostate cancer. Purpose: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.

Detailed Description
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Objectives: I. Compare the time to progression, time to development of disease-related pain, and incidence of grade 3 or worse treatment-related adverse events in patients with asymptomatic metastatic hormone refractory adenocarcinoma of the prostate treated with APC8015 versus control infusion. II. Compare response rate and duration of response in these patients. Outline: This is a randomized study. Patients are randomized to one of two treatment arms. Arm I: Autologous dendritic cell precursors (ADCP) are harvested on weeks 0, 2, and 4. Patients receive APC8015 comprised of ADCP activated with prostatic acid phosphatase-sargramostim (GM-CSF) fusion protein IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Arm II: ADCP are harvested as in arm I. Patients receive unactivated ADCP IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Pain is assessed weekly for up to 3 years or until 4 weeks after objective disease progression. Patients are followed monthly for up to 3 years or until disease progression. At the time of disease progression, patients treated on arm II may receive treatment on Protocol D9903. Projected Accrual: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study.

Official Title
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A Randomized, Double Blind, Placebo Controlled Trial of Immunotherapy With Autologous Antigen-Loaded Dendritic Cells (Provenge) for Asymptomatic Metastatic Hormome-Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: sipuleucel-T
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Metastatic disease as evidenced by soft tissue and/or bony metastases. Baseline PSA value of at least 5 ng/mL. All subjects must have stable or rising PSA. Tumor progression after hormonal therapy. Hormonal therapy consisting of castration by orchiectomy or LHRH agonists for treatment of prostate cancer. Castration levels of testosterone (< 50 ng/dL) must be documented for all subjects including subjects who underwent orchiectomy as therapy for cancer of the prostate. A subject is eligible if he initially responded to antiandrogen withdrawal (> 25% decrease in PSA) but at the time of registration demonstrated tumor progression. A subject is eligible if he failed to respond to antiandrogen withdrawal. Subjects have no cancer-related pain and do not regularly require analgesics for cancer-related pain. ECOG Performance Status of 0 or 1. Life expectancy of at least 16 weeks. Adequate hematologic, renal, and liver function. Exclusion Criteria include: Visceral organ metastases (e.g., liver, lung, brain) or cytologically positive effusions (e.g., pleural effusions or ascites). Metastatic disease expected to be in need of radiation therapy within 4 months. Concurrent therapy with experimental agents. Systemic corticosteroids at doses greater than 40 mg hydrocortisone per day for any reason other than treatment of prostate cancer within the previous 6 months without prior approval. Please note that there are additional eligibility criteria. The study center will determine if you meet all of the criteria.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sipuleucel-T<br> | Biological: sipuleucel-T<br>* Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.<br>* Other names: APC8015, Provenge;|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Approximately one-third of the autologous quiescent antigen presenting cells (APCs) prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Objective Disease Progression | The time to objective disease progression in patients with asymptomatic metastatic hormone-refractory prostate cancer treated with APC8015 (sipuleucel-T). | 36 months from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival | From randomization to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer