RATIONALE: Vaccines made from a gene-modified virus may make the body build an effective
immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune
response and prevent or delay the recurrence of cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in
patients with progressive or locally recurrent prostate cancer.
- Determine the clinical safety and feasibility of vaccine therapy comprising priming
vaccinations of vaccinia-PSA-TRICOM and recombinant fowlpox-GM-CSF (rF-GM-CSF) followed
by boosting vaccinations of fowlpox-PSA-TRICOM with or without rF-GM-CSF in patients
with progressive or locally recurrent prostate cancer.
OUTLINE: This is a dose-escalation study of booster vaccinations comprising
vaccinia-PSA-TRICOM (rV-PSA-TRICOM) with or without recombinant fowlpox-GM-CSF (rF-GM-CSF).
Patients are assigned to 1 of 5 groups.
- Groups 1 and 2: Patients receive priming vaccinations comprising rV-PSA-TRICOM
subcutaneously (SC) and rF-GM-CSF SC on day 1. Patients also receive a booster
vaccination comprising fowlpox-PSA-TRICOM (rF-PSA-TRICOM) by intraprostatic (IP)
injection on days 29, 57, and 85.
- Groups 3 and 4: Patients receive priming and booster vaccinations as in groups 1 and 2.
Patients also receive a booster vaccination comprising rF-GM-CSF IP on days 29, 57, and
85.
- Group 5: Patients receive priming and booster vaccinations as in groups 3 and 4.
Patients also receive booster vaccinations comprising rF-PSA-TRICOM SC and rF-GM-CSF SC
on days 29, 57, and 85.
Cohorts of 3-6 patients in each group receive escalating doses of booster vaccinations
comprising rF-PSA-TRICOM with or without rF-GM-CSF until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients
experience dose-limiting toxicity.
Treatment in all groups continues in the absence of unacceptable toxicity or disease
progression.
PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 30 months.
DISEASE CHARACTERISTICS:
- Histologically confirmed* adenocarcinoma of the prostate, meeting 1 of the following
criteria:
- Locally recurrent disease after prior local radiotherapy or cryotherapy, defined
as 3 consecutive rising prostate-specific antigen levels AND confirmed by biopsy
performed ≥ 18 months after completion of radiotherapy
- Not a candidate for or refused local definitive therapy (surgery or radiation
therapy) AND had clinically progressive disease during androgen deprivation
therapy, defined as 3 increases in PSA over nadir, separated by ≥ 1 week NOTE:
*Patients without a pathological specimen available are eligible provided there
is histologic diagnosis of prostate cancer and a clinical course consistent with
prostate disease
- Minimal extraprostatic disease allowed
- No clinically active brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 6 months
Hematopoietic
- Granulocyte count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Lymphocyte count ≥ 500/mm^3
- Hemoglobin ≥ 10 g/dL
Hepatic
- Bilirubin < 1. 5 mg/dL (≤ 3. 0 mg/dL for patients with Gilbert's syndrome)
- AST and ALT < 2. 5 times upper limit of normal
- Hepatitis B and C negative
Renal
- Creatinine < 2. 0 mg/dL OR creatinine clearance > 60 mL/min
- No proteinuria, defined as ≥ 1,000 mg of protein on 24-hour urine collection
- No abnormal urine sediment or hematuria unless the underlying cause is determined to
be non-renal
Cardiovascular
- No New York Heart Association class II-IV heart disease
- No objective evidence of congestive heart failure by physical exam or imaging
Pulmonary
- No pulmonary disease that causes fatigue or dyspnea during ordinary physical activity
Neurologic
- No history of seizures
- No history of encephalitis
- No history of multiple sclerosis
Gastrointestinal
- No inflammatory bowel disease
- No Crohn's disease
- No ulcerative colitis
- No active diverticulitis
Immunologic
- HIV negative
- History of autoimmunity not requiring systemic immunosuppressive therapy and not
threatening vital organ function (e. g., CNS, heart, lungs, kidneys, skin, or
gastrointestinal tract) allowed
- No 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
- Graves' disease
- No other altered immune function, including any of the following conditions:
- History of or active eczema or other eczematoid skin disorders
- Atopic dermatitis
- Other skin diseases
- Open wounds
- No history of allergy or untoward reaction to prior vaccination with vaccinia virus or
any component of study treatment
- No serious hypersensitivity to egg products
Other
- Fertile patients must use effective contraception during and for at least 4 months
after study treatment
- Able to avoid close household contact with any of the following for at least 3 weeks
after each study vaccination:
- Individuals with a history of or active eczema or other eczematoid skin
disorders
- Individuals with acute, chronic, or exfoliative skin conditions (e. g., atopic
dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes
or wounds) until the condition resolves
- Pregnant or nursing women
- Children age 3 and under
- Immunodeficient or immunosuppressed (by disease or therapy) individuals,
including HIV-positive individuals
- No other malignancy within the past year except nonmelanoma skin cancer or carcinoma
in situ of the bladder
- No other life-threatening illness
- No other serious medical illness that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior vaccinia unless immune to vaccinia
- No other concurrent immunotherapy
Chemotherapy
- No concurrent anticancer chemotherapy
Endocrine therapy
- See Disease Characteristics
- No steroid eye drops for at least 2 weeks before, during, and for at least 4 weeks
after study treatment
- Concurrent hormonal therapy allowed
- No concurrent systemic steroids, including glucocorticoids, except for physiologic
doses for systemic steroid replacement or local (i. e., topical, nasal, or inhaled)
steroid use
Radiotherapy
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
- At least 4 weeks since prior surgery
- No prior splenectomy
- No concurrent major surgery
Other
- Recovered from all prior therapy
