GM-CSF in Treating Patients With Relapsed Prostate Cancer

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Biological: sargramostim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00908141

8201 (Other Identifier)

CASE6805 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Colony stimulating factors, such as GM CSF, may increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known which GM-CSF regimen is more effective in treating patients with prostate cancer.

PURPOSE: This randomized phase II trial is studying how well GM-CSF works in treating patients with relapsed prostate cancer.

Full description

OBJECTIVES:

Primary

• To determine the ability of sargramostim (GM-CSF) to increase the number and activation of dendritic cells (DC) in patients with biochemically relapsed prostate cancer.

Secondary

• To determine the effect of administration schedule and hormonal state on sargramostim-induced DC number and activation in these patients.
• To correlate the effects of sargramostim on DC number and activation with effects on prostate-specific antigen (PSA) modulation.
• To determine whether sargramostim administration generates antiprostate cancer immune responses in these patients.

OUTLINE: Patients are stratified according to hormonal status (androgen-dependent vs androgen-independent). Patients are then randomized to 1 of 2 treatment arms.

• Arm I: Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive GM-CSF SC three times weekly for 4 weeks. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for dendritic cell (DC) number by flow cytometry, DC activation by quantitative real-time polymerase chain reaction (QRT-PCR), and immunity by serological analysis of recombinant cDNA expression libraries (SEREX).

Enrollment: 17 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Non-metastatic, recurrent systemic disease as manifested by a rising PSA, defined as ≥ 2 consecutive rises in PSA to be documented over a reference value (measure 1)

    • The first rising PSA (measure 2) should be at taken ≥ 14 days after the reference value

    • A third confirmatory PSA measure is required (second beyond the reference level) to be greater than the second, and it must be obtained ≥ 14 days after the second measure

      • If this is not the case, a fourth PSA is required to be taken and be greater than the second measure

    • No local-only relapse

• Must have undergone prior definitive therapy for prostate cancer consisting of external beam radiotherapy, brachytherapy (with or without external beam radiotherapy), or radical prostatectomy (with or without adjuvant androgen ablation)

  • Patients who have not undergone definitive therapy as above or who have undergone hormonal therapy alone are not eligible

• No evidence of metastases on bone or CT scan

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Leukocytes ≥ 3,000/μl
• Absolute neutrophil count ≥ 1,500/μl
• Platelets ≥ 100,000/μl
• Total bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine ≤ 1.5 times ULN
• No active thrombophlebitis or disseminated intravascular coagulopathy
• No history of pulmonary embolus
• No history of immunodeficiency or autoimmune diseases
• No uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy for any reason

• No concurrent anticoagulation therapy (i.e., therapeutic coumadin)

  • Prophylactic anticoagulation (e.g., aspirin) allowed

• No concurrent systemic corticosteroids or other immunosuppressives

  • Inhaled or topical steroids allowed

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

Arm I: sargramostim (days1-14)

Experimental group

Description:

Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-14. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Biological: sargramostim

Arm II: sargramostim (3xweek)

Experimental group

Description:

Patients receive GM-CSF SC three times weekly for 4 weeks. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Treatment:

Biological: sargramostim