Clinical trial NCT00305669: GM-CSF Before Surgery in Treating Patients With Localized Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-03-22
Enrollment: 24
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Determine the safety and tolerability of daily neoadjuvant sargramostim (GM-CSF) in patients with localized prostate cancer undergoing radical prostatectomy.
timeFrame: up to 6 weeks following surgery
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Lawrence Fong, MD
role: STUDY_CHAIR
References: