GM-CSF Before Surgery in Treating Patients With Localized Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Colony-stimulating factors, such as GM-CSF, may help the body build an effective immune response to kill tumor cells. Giving GM-CSF before surgery may be an effective treatment for localized prostate cancer. PURPOSE: This clinical trial is studying how well giving GM-CSF before surgery works in treating patients with localized prostate cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety and tolerability of daily neoadjuvant sargramostim (GM-CSF) in patients with localized prostate cancer undergoing radical prostatectomy. Determine whether tissue-specific antiprostate cancer immunity is induced by the administration of neoadjuvant GM-CSF in patients with localized prostate cancer prior to radical prostatectomy. Secondary Estimate the baseline antitumor immune response in patients treated with 2 different dose schedules of GM-CSF. Determine the magnitude of the difference in immune response between 2 dose schedules of GM-CSF. Determine the clinical effects, including prostate-specific antigen (PSA) decline, surgical outcome, surgical complications, and histologic appearance of surgical specimen, of this regimen in these patients. OUTLINE: This is a pilot study. Patients are stratified according to sargramostim (GM-CSF) dose. Patients receive 1 of 2 dose levels of GM-CSF subcutaneously on days 1-14 or 1-21. Treatment continues in the absence of unacceptable toxicity. Within 3 days after the last dose of GM-CSF, patients undergo radical prostatectomy. Blood is collected at baseline, day 28 of each course, and at the 4-week follow-up visit and is examined for activated T-cells. Tissue is collected during surgery and assessed for biomarkers and cytokines. After completion of study treatment, patients are followed at 4 weeks. PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Official Title
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A Pilot Study of Two Dose Schedules of Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) as Neo-Adjuvant Therapy in Patients With Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: sargramostim
* Other: immunohistochemistry staining method
* Other: immunological diagnostic method
* Other: laboratory biomarker analysis
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the prostate No neuroendocrine or small cell features No evidence of metastatic disease Planning radical prostatectomy at least 2 months from now Testosterone level normal PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 or Karnofsky PS 70-100% Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8 g/dL AST and ALT ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN Creatinine ≤ 1.5 times ULN PT and PTT normal Fertile patients must use effective barrier contraception No history of allergic reaction to compounds of similar chemical or biologic composition to sargramostim (GM-CSF) No ongoing or active bacterial, viral, or fungal infection DLCO > 50% if patient has a history of clinically significant obstructive airway disease No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No other active malignancy, defined as cancer for which therapy has been completed and patient is now considered < 30% risk of relapse, except nonmelanoma skin cancer No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness No underlying medical condition that, in the opinion of the principal investigator, may make the administration of GM-CSF hazardous or obscure the interpretation of adverse events PRIOR CONCURRENT THERAPY: More than 4 weeks since prior major surgery No prior radiotherapy, immunotherapy, chemotherapy, or other investigational therapy for this cancer No prior hormonal therapy including any of the following: Luteinizing-hormone releasing hormone (LHRH) agonists LHRH antagonists Antiandrogens, including any of the following: Bilcalutamide Flutamide Nilutamide 5-alpha-reductase inhibitors PC-SPES or other PC-x product Estrogen-containing nutriceuticals No concurrent chemotherapy or radiotherapy No concurrent systemic steroid therapy Concurrent inhaled or topical steroids allowed No other concurrent immunotherapy No other concurrent investigational agent No other concurrent anticancer agents or therapies
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF before surgery<br>GM-CSF dose prior to surgery- Cohort 1-GM-CSF 250mcg/m2 for 2 weeks Cohort 2-GM-CSF 250mcg/m2 for 3 weeks Cohort 3-GM-CSF 250mcg/m2 for 4 weeks Cohort 4-GM-CSF 125mcg/m2 for 4 weeks | Biological: sargramostim<br> <br> Other: immunohistochemistry staining method<br> <br> Other: immunological diagnostic method<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety and tolerability of daily neoadjuvant sargramostim (GM-CSF) in patients with localized prostate cancer undergoing radical prostatectomy. |  | up to 6 weeks following surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer