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Prostatic Acid Phosphatase-Sargramostim Fusion Protein or Sargramostim in Treating Patients with Non-Metastatic Prostate Cancer

Trial Status: Closed to Accrual

This randomized phase II trial studies how well vaccine therapy or sargramostim works in treating patients with prostate cancer that has not spread to other places in the body (non-metastatic). Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer.

Inclusion Criteria

  • Patients with a histologic diagnosis of adenocarcinoma of the prostate
  • Patients must have completed local therapy by surgery and/or ablative radiation therapy at least 3 months prior to entry, with removal or ablation of all visible disease, including seminal vesical and/or local lymph node involvement
  • Patients must have high-risk clinical stage D0 disease defined by the following: * In patients previously treated by prostatectomy, must have evidence of rising prostate specific antigen (PSA) with measurements at least two weeks apart, and final serum PSA value must be >= 2 ng/mL * In patients previously treated with ablative radiation therapy, an absolute increase in serum PSA by at least 2 ng/mL over nadir PSA value after radiation therapy * All patients must have at least four serum PSA values determined over a 12-week-to-six-month period of time prior to study entry from the same clinical laboratory; all available PSA values during this period (up to 6 months) will be used to calculate a PSA doubling time, according to the Memorial Sloan-Kettering Cancer Center nomogram * The PSA doubling time calculated from this nomogram, up to and including the value obtained at screening, must be < 12 months
  • Patients with a prior history of a second malignancy are eligible provided they have been treated with curative intent and have been free of disease greater than three years; there will be no exclusion for patients with a history of basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma that has been adequately treated
  • Patients who are sexually active must use a reliable form of contraception while on study and for 4 weeks after the last immunization
  • Eastern Cooperative Oncology Group (ECOG) performance score < 2 and life expectancy of at least 4 months
  • White blood cells (WBC) >= 3000/mm^3
  • Hematocrit >= 30%
  • Platelet count >= 100,000/mm^3
  • Serum creatinine =< 1.5 mg/dl or a calculated creatinine clearance >= 60 cc/min
  • Serum bilirubin =< 2.0 mg/dl, within 4 weeks prior to first immunization
  • Patients must be informed of the experimental nature of the study and its potential risks and must sign an institutional review board (IRB)-approved written informed consent form indicating such an understanding
  • Willingness to provide blood samples for immune studies, per study calendar, up to one year after study, even if off study

Exclusion Criteria

  • Small cell or other variant prostate cancer histology
  • Patients cannot have evidence of immunosuppression or have been treated with immunosuppressive therapy, such as chemotherapy or chronic treatment dose corticosteroids (greater than the equivalent of 10 mg prednisone per day), within 6 months of the first vaccination; treatment or salvage radiation therapy must have been completed at least 4 weeks prior to the first vaccination
  • Seropositive for human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C (HCV) per patient history
  • Prior treatment with an luteinizing hormone-releasing hormone (LHRH) agonist or nonsteroidal antiandrogen, except in the following circumstances: Neoadjuvant/adjuvant androgen deprivation therapy administered with radiation therapy or at the time of prostatectomy is acceptable, provided that there was no evidence of PSA progression while on treatment; in this situation, patients must not have received more than 24 months of androgen deprivation treatment, and must not have been treated within 12 months prior to screening; other treatment with androgen deprivation therapy is prohibited
  • Serum testosterone at screening < 50 ng/dL
  • Patients must not be concurrently taking other medications or supplements with known hormonal effects, including PC-SPES, megestrol acetate, finasteride, ketoconazole, estradiol, or Saw Palmetto; all other medications with possible anti-cancer effects must be discussed with the principal investigator (PI) prior to study entry
  • Patients previously treated with herbal supplements, or other potential or experimental therapies for prostate cancer must have discontinued these treatments and completed at least a one-month washout prior to beginning treatment
  • FOR FIRST COHORT ONLY, NOT REQUIRED FOR BIOMARKER COHORT: Patients will be allowed to eat pomegranates and drink pomegranate juice provided that the patient has been taking these for 4 weeks or more with evidence of progressive disease as outlined above; these patients should be instructed to continue to take pomegranates and/or pomegranate juice as per the same schedule while on study; documentation of amount and duration will be captured for those patients taking pomegranates or pomegranate juice; those patients who have not been taking pomegranates or pomegranate juice prior to study entry will not be allowed to begin these while on study
  • Patients must not have evidence of bone metastases or lymph node involvement as determined by bone scan or computed tomography (CT) scan of the abdomen and pelvis within 4 weeks of study entry; Note: NaF-PET/CT scan information will NOT be used to determine evidence of metastases for eligibility purposes or for defining disease progression
  • Patients must not have been treated with a prior vaccine therapy for prostate cancer
  • Patients must not have known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol
  • Patients must not have known allergic reactions to GM-CSF
  • Patients with unstable or severe intercurrent medical conditions or laboratory abnormalities that would impart, in the judgment of the Medical Monitor, excess risk associated with study participation or study agent administration
  • Patients cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies


San Francisco
UCSF Medical Center-Mount Zion
Contact: Lawrence Fong
Phone: 415-514-3160


Johns Hopkins University / Sidney Kimmel Cancer Center
Contact: Emmanuel S. Antonarakis
Phone: 410-955-8804


University of Wisconsin Hospital and Clinics
Contact: Douglas G. McNeel
Phone: 608-263-4198


I. To evaluate the 2-year metastasis-free survival of patients with non-metastatic prostate cancer (clinical stage D0) treated with a DNA vaccine encoding prostatic acid phosphatase (PAP), with sargramostim (GM-CSF) as an adjuvant, versus patients treated with GM-CSF only.


I. To evaluate if immunization with a DNA vaccine encoding PAP prolongs prostate specific antigen (PSA) doubling time in patients with non-metastatic prostate cancer.

II. To evaluate the safety and tolerability of the prostatic acid phosphatase-sargramostim fusion protein (pTVG-HP) DNA vaccine administered to patients with clinical stage D0 prostate cancer.

III. To evaluate the median progression-free survival, and PSA progression-free survival, of patients with non-metastatic prostate cancer (clinical stage D0) treated with a DNA vaccine encoding PAP, with GM-CSF as an adjuvant, versus patients treated with GM-CSF only.


I. To determine if immunization with a DNA vaccine encoding PAP elicits antigen-specific T-cell and/or immunoglobulin (Ig)G responses.

II. To determine if immune monitoring of T-cell responses can be accurately and reproducibly conducted in a multi-center vaccine trial.

III. To determine if the development of PAP-specific T-cell immune responses are associated with clinical responses.

IV. To determine if baseline immune responses specific for PAP are predictive (or not) for the development of PAP-specific T-cells and/or are associated with 2-year metastasis-free survival in the cohort of patients who receive a DNA vaccine encoding PAP. (Expanded subject cohort)

V. To determine if antigen spread (the development of immune responses to other cancer-associated proteins) is associated with 2-year metastasis-free survival. (Expanded subject cohort)

VI. To determine if Quantitative Total Bone Imaging (QTBI) by sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) can identify bone lesions in this patient population not detected by standard bone scintigraphy. (Expanded subject cohort)

VII. To determine whether the presence of lesions detected by NaF PET/CT at baseline is associated with early disease progression (within 1 year) by standard radiographic imaging methods (CT and bone scintigraphy). (Expanded subject cohort)

VIII. To determine if growth rates, and changes in growth rates, determined by NaF PET/CT are associated with PSA doubling time and changes in PSA doubling time. (Expanded subject cohort)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM 1: Patients receive plasmid DNA encoding human prostatic acid phosphatase (PAP) (pTVG-HP) intradermally (ID) and sargramostin ID every 2 weeks for 12 weeks (6 doses total). Treatment then continues every 3 months for up to 7 vaccinations in the absence disease progression or unacceptable toxicity.

ARM 2: Patients receive sargramostim ID as in Arm 1. Treatment then continues every 2 weeks, every month, or every 3 months (as determined by patient's immune response) for up to 7 vaccinations in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for up to 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Wisconsin Hospital and Clinics

Principal Investigator
Douglas G. McNeel

  • Primary ID CO08801
  • Secondary IDs NCI-2011-00965, H-2008-0073
  • ID NCT01341652