Vaccine Therapy and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Treating Patients With Prostate Cancer That Progressed After Surgery and/or Radiation Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00108732
First received: April 18, 2005
Last updated: February 25, 2013
Last verified: February 2013

April 18, 2005
February 25, 2013
February 2006
October 2010   (final data collection date for primary outcome measure)
Proportion of Patients Free of PSA Progression at 6 Months (Prior to the Start of Androgen Ablation) [ Time Frame: Assessed at 6 months ] [ Designated as safety issue: No ]

For patients who achieved a > 50% decline in PSA, an increase in PSA value by 50% over the nadir, confirmed by a second PSA two weeks later is considered progressive disease. The PSA rise must be at least 5 ng/mL or back to pretreatment baseline, whichever is greater.

Changes in PSA below 5 ng/mL will not be considered assessable for progression.

For patients whose PSA has not decreased by 50%, an increase in PSA value > 50% of baseline (on trial) or nadir PSA, whichever is lower, confirmed by a repeat PSA two weeks later is considered progressive disease. The PSA must have risen by at least 5 ng/mL.

Not Provided
Complete list of historical versions of study NCT00108732 on ClinicalTrials.gov Archive Site
  • Proportion of Patients With PSA Response [ Time Frame: Assessed monthly during the first 24 weeks and then every 3 months for a maximum total of 24 months ] [ Designated as safety issue: No ]

    PSA response is defined as complete biochemical response or partial response.

    Complete Response:

    A PSA < 0.2 ng/mL confirmed by a repeat PSA one month later is considered a complete biochemical response for patients with prior radical prostatectomy. A PSA < 1 ng/mL on three separate occasions taken at least one month apart is considered a complete biochemical response in patients with radiation therapy only.

    Partial Response:

    A reduction in PSA by > 50% from baseline, confirmed by repeat PSA 1 month later.

  • Difference Between Day 4 PSA Level and Day 15 PSA Level [ Time Frame: Assessed at day 4 and day 15 of cycle 1 ] [ Designated as safety issue: No ]
    PSA level was assessed on Day 4 and Day 15 of cycle 1, and a comparison between the two measurements was done.
  • The Difference Between PSA Slopes Before and After Treatment [ Time Frame: Assessed monthly during the first 24 weeks and then every 3 months for a maximum total of 24 months ] [ Designated as safety issue: No ]
    PSA slopes were assessed by multiple PSA values obtained prior to registration and during treatment. Only patients who completed at least 3 months of treatment were included in this analysis. The PSA slopes were calculated by a piecewise linear model using the three or four PSA values obtained prior to registration and PSA measurements obtained every 4 weeks for the first six months of treatment. Natural log transformed PSA levels were used in this analysis, and the difference between PSA slopes before and after treatment was calculated.
Not Provided
Not Provided
Not Provided
 
Vaccine Therapy and Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Treating Patients With Prostate Cancer That Progressed After Surgery and/or Radiation Therapy
A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With Prostate-Specific Antigen (PSA) Progression After Local Therapy for Prostate Cancer

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Androgens can cause the growth of prostate cancer cells. Drugs, such as bicalutamide and goserelin, may stop the adrenal glands from making androgens in patients whose tumor cells continue to grow. Giving vaccine therapy together with GM-CSF and, when needed, androgen ablation may be a more effective treatment for prostate cancer.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with GM-CSF works in treating patients with prostate cancer that progressed after surgery and/or radiation therapy.

OBJECTIVES:

Primary

  • To evaluate the effect of PROSTVAC-V/TRICOM (Vaccinia) on cycle 1 followed by PROSTVAC-F/TRICOM (Fowlpox) and GM-CSF on biochemical PSA progression at 6 months.

Secondary

  • To determine the change in PSA velocity pre-treatment to post-treatment.
  • To evaluate the percentage of patients experiencing a >50% decline in serum PSA repeated at 4 weeks.
  • To evaluate tolerability and any toxicity related to treatment with PSA vaccine and GM-CSF.
  • To determine the effect of GM-CSF on PSA immediately after treatment (day 4) compared to a delayed effect (day 15).

OUTLINE: This is a multicenter study.

Patients receive vaccinia-PSA-TRICOM vaccine subcutaneously (SC) on day 1 and sargramostim (GM-CSF) SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox-PSA-TRICOM vaccine SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox-PSA-TRICOM vaccine and GM-CSF repeats every 4 weeks for 2 courses (weeks 5 and 9). Beginning in week 13, patients receive fowlpox-PSA-TRICOM vaccine and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity.

Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox-PSA-TRICOM vaccine and GM-CSF. Treatment continues in the absence of further clinical or biochemical disease progression.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 10 years.

ACTUAL ACCRUAL: A total of 50 patients were accrued for this study.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Biological: vaccinia
    Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1.
    Other Name: PROSTVAC-V/TRICOM
  • Biological: GM-CSF

    Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity.

    Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.

    Other Name: sargramostim
  • Biological: fowlpox

    Beginning with cycle 2, patients receive fowlpox subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity.

    Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.

    Other Name: PROSTVAC-F/TRICOM
  • Drug: bicalutamide
    Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
    Other Name: Casodex
  • Drug: goserelin
    Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.
    Other Name: Zoladex
Experimental: Vaccinia/Fowlpox/GM-CSF

Patients receive vaccinia subcutaneously (SC) on day 1 and GM-CSF SC on days 1-4 during cycle 1. Beginning with cycle 2, patients receive fowlpox SC on day 1 and GM-CSF SC on days 1-4. Treatment with fowlpox and GM-CSF repeats every 4 weeks for 2 courses. Beginning in week 13, patients receive fowlpox and GM-CSF as above every 12 weeks in the absence of clinical or biochemical disease progression or unacceptable toxicity.

Patients with biochemical or clinical disease progression may start androgen ablation therapy comprising oral bicalutamide once daily for 1 month and goserelin SC once every 4 weeks in addition to fowlpox vaccine and GM-CSF until further progression or a max of 12 months.

Interventions:
  • Biological: vaccinia
  • Biological: GM-CSF
  • Biological: fowlpox
  • Drug: bicalutamide
  • Drug: goserelin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
January 2023
October 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed prostate cancer and tumors limited to the prostate

    • Seminal vesical involvement allowed provided all visible disease has been surgically removed
  • Prior treatment with definitive surgery or radiation therapy or both
  • At least 1 year since prior neoadjuvant/adjuvant chemotherapy or hormonal therapy
  • More than 1 year since prior testosterone level-modulating therapy, such as LHRH agonists/antagonists and antiandrogens
  • Hormone-sensitive disease as evident by a serum total testosterone level > 150 ng/dL within 4 weeks prior to registration
  • Evidence of PSA progression after completion of definitive surgery and/or radiotherapy, as demonstrated by all of the following:

    • Three consecutively rising PSA values within the past 6 months, each obtained ≥ 4 weeks apart
    • Most recent PSA value > 0.4 ng/mL (after prostatectomy) OR > 1.5 ng/mL (after radiotherapy)
    • PSA doubling time < 12 months
  • ECOG PS of 0-1
  • Age of 18 and over
  • WBC ≥ 3,000/mm^3
  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Urine protein < 1,000 mg by 24-hour urine collection AND no evidence of chronic renal disease (Creatinine normal or Creatinine clearance ≥ 60 mL/min)
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal
  • Alkaline phosphatase normal
  • Hepatitis B and hepatitis C negative
  • PT/INR normal
  • Human immunodeficiency virus sero-negative
  • Recovered from prior therapy
  • Patients must use a safe and effective method of contraception to prevent virus transmission
  • Patients must agree to avoid fathering a child and use a latex barrier with adequate contraception prior to study entry and for at least 4 months following the last vaccine injection
  • All sites of disease must be evaluated within 4 weeks prior to registration
  • Recovered from any other illness
  • Must be able to avoid close contact (i.e., shares the same house or has close physical contact) with any of the following individuals for ≥ 3 weeks after treatment with the study vaccinia vaccine:

    • Individuals with a history of or active eczema, atopic dermatitis, Darier's disease
    • Individuals with other acute, chronic, or exfoliative skin condition, including any of the following:

      • Burns
      • Impetigo
      • Varicella zoster
      • Severe acne
      • Contact dermatitis
      • Psoriasis
      • Herpes
      • Other open rashes or wounds
    • Pregnant or nursing women
    • Children ≤ 3 years of age
    • Immunodeficient or immunosuppressed individuals either by disease or therapy, including HIV-positive individuals
  • Concurrent thyroid hormone-replacement therapy allowed

Exclusion Criteria:

  • Lymph node involvement
  • Metastatic disease by physical exam, CT scan, MRI, or bone scan within 4 weeks of registration
  • Prior vaccine therapy or immunotherapy for prostate cancer
  • Administration of any of the following agents during the period in which the PSA levels are collected:

    • 5α-reductase inhibitors
    • Ketoconazole
    • Megestrol acetate
    • Systemic steroids
    • Herbal products
  • Proteinuria or abnormal sediment by urine analysis
  • Active autoimmune disease, including any of the following:

    • Addison's disease
    • Hashimoto's thyroiditis
    • Systemic lupus erythematosus
    • Sjögren's syndrome
    • Scleroderma
    • Myasthenia gravis
    • Goodpasture's syndrome
    • Active Graves' disease
  • History of autoimmune disease that has required systemic immunosuppressive therapy or has impaired central nervous system (CNS), heart, lung, kidney, skin, or gastrointestinal tract function
  • Concurrent systemic steroids

    • Local (e.g., topical, nasal, inhaled) steroids allowed

      • No steroid eye drops for ≥ 2 weeks before and ≥ 4 weeks after vaccinia vaccination
  • Receiving other investigational agents or concurrent anticancer therapy
  • Uncontrolled intercurrent illness
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situation that would preclude study compliance
  • Clinically significant cardiomyopathy
  • Significant allergy or hypersensitivity to eggs
  • History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the study vaccinia vaccine regimen
  • History of or active eczema
  • Ongoing, active infection
  • Atopic dermatitis
  • Darier's disease
  • Other acute, chronic, or exfoliative skin condition, including any of the following:

    • Burns
    • Impetigo
    • Varicella zoster
    • Severe acne
    • Contact dermatitis
    • Psoriasis
    • Herpes
    • Other open rashes or wounds
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00108732
NCI-2012-03075, U10CA021115, E9802, CDR0000422430
No
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Study Chair: Robert S. DiPaola, MD Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP