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

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 1

Conditions: Prostate Cancer

Treatments: Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Biological: sargramostim; Procedure: conventional surgery; Procedure: neoadjuvant therapy; Other: immunological diagnostic method

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00305669

UCSF-04558

CDR0000455649

UCSF-H40568-25161-02B

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 24 patients

Sex: Male

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

GM-CSF before surgery

Experimental group

Description:

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

Treatment:

Procedure: conventional surgery

Procedure: neoadjuvant therapy

Other: laboratory biomarker analysis

Other: immunohistochemistry staining method

Biological: sargramostim

Other: immunological diagnostic method