GM-CSF in Treating Patients With Relapsed Prostate Cancer

Immunologic Effects of GM-CSF (Sargramostim, Leukine®) in Patients With Biochemically-relapsed Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: sargramostim

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I: sargramostim (days1-14); 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.	Biological: sargramostim; Given subcutaneously on varying schedule
Experimental: Arm II: sargramostim (3xweek); 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.	Biological: sargramostim; Given subcutaneously on varying schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate Specific Antigen (PSA) Response	The number of patients with PSA modulation defined as PSA decline of at least 50%	post treatment at 9 weeks

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert Dreicer, MD, FACP, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: May 22, 2009
• First Submitted That Met QC Criteria: May 22, 2009
• First Posted (Estimate): May 25, 2009

Study Record Updates

• Last Update Posted (Estimate): August 23, 2013
• Last Update Submitted That Met QC Criteria: August 15, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: CASE6805 (Other Identifier: Case Comprehensive Cancer Center); P30CA043703 (U.S. NIH Grant/Contract); 8201 (Other Identifier: Cleveland Clinic IRB)