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GM-CSF in Treating Patients With Relapsed Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00908141
First received: May 22, 2009
Last updated: September 18, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
 Biological: sargramostim
 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunologic Effects of GM-CSF (Sargramostim, Leukine®) in Patients With Biochemically-relapsed Prostate Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Dendritic cell (DC) activation index post-sargramostim vs pre-sargramostim [ Time Frame: pre-tx and q 2 weeks during tx and post tx ] [ Designated as safety issue: No ]
    DC (lin- CD4+) will be purified from peripheral blood using a magnetic cell sorting kit. The number of DC isolated will be expressed per ml of blood. (This will provide an independent method of quantifying total DC population). Activation of the cells separated will be evaluated by assessing the ratio of IL-12(p40) to IL-10 mRNA as quantified by QRT-PCR. A DC activation index will be calculated for each sample by multiplying the number of DC per ml of blood by the ratio of IL-12/IL-10 mRNA expressed.


Secondary Outcome Measures:
  • Effect of schedule and hormonal state on DC activation index [ Time Frame: pre-tx andq2 weeks during tx and post-tx ] [ Designated as safety issue: No ]
    DC (lin- CD4+) will be purified from peripheral blood using a magnetic cell sorting kit. The number of DC isolated will be expressed per ml of blood. (This will provide an independent method of quantifying total DC population). Activation of the cells separated will be evaluated by assessing the ratio of IL-12(p40) to IL-10 mRNA as quantified by QRT-PCR. A DC activation index will be calculated for each sample by multiplying the number of DC per ml of blood by the ratio of IL-12/IL-10 mRNA expressed.

  • PSA modulation with therapy [ Time Frame: pre and post tx and q 4 weeks during tx ] [ Designated as safety issue: No ]
    Patients will have PSA measured at baseline and monthly thereafter. PSA modulation will be recorded as absolute declines in PSA values and PSA doubling time (PSADT) pre- and post-therapy (calculated using MSK nomogram)


Enrollment: 17
Study Start Date: October 2005
Study Completion Date: July 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 Biological: sargramostim
Given subcutaneously on varying schedule
Experimental: 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.
 Biological: sargramostim
Given subcutaneously on varying schedule

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00908141

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Robert Dreicer, MD, FACP Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00908141     History of Changes
Other Study ID Numbers: CASE6805, P30CA043703, CASE6805, 8201
Study First Received: May 22, 2009
Last Updated: September 18, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:
adenocarcinoma of the prostate
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
 Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on May 19, 2013