Vaccine Therapy With or Without Docetaxel in Treating Patients With Metastatic Prostate Cancer

OBJECTIVES:

• Compare the relative change in prostate-specific antigen (PSA)-specific T-cell precursors (CD8) from baseline to day 85 in patients with metastatic androgen-independent prostate cancer treated with a vaccination regimen comprising fowlpox-PSA vaccine, recombinant rV-B7.1 vaccine, recombinant vaccinia-PSA vaccine, and sargramostim (GM-CSF) with or without docetaxel.
• Compare the safety of these regimens in these patients.
• Compare clinical activity of these regimens in these patients.
• Determine the immunologic effects in these patients after additional vaccine/chemotherapy courses.
• Measure CD4 T-cell responses to the vaccine in these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms after receiving priming vaccinations.

• Priming vaccinations: All patients receive recombinant vaccinia-prostate-specific antigen (PSA) vaccine subcutaneously (SC) and recombinant rV-B7.1 vaccine SC on day 1 and sargramostim (GM-CSF) SC on days 1-4. Patients then receive fowlpox-PSA vaccine (F-PSA) SC on day 15 and GM-CSF SC on days 15-18.
• Arm I: Patients receive docetaxel IV over 30 minutes on days 29, 36, and 43; F-PSA SC on day 30; and GM-CSF SC on days 30-33. Treatment repeats beginning on day 56 for one more course. Patients who do not have disease progression at day 85 receive docetaxel weekly for 3 weeks and F-PSA on day 1 of each course. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive F-PSA SC on days 29 and 57 and GM-CSF SC on days 29-32 and 57-60. Patients who show disease progression after day 85 either radiographically or by rising PSA stop receiving the vaccine and may receive docetaxel weekly for 3 weeks. Chemotherapy repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 28 patients (14 per treatment arm) will be accrued for this study within 9-10 months.

DISEASE CHARACTERISTICS:

• Diagnosis of androgen-independent metastatic adenocarcinoma of the prostate, confirmed by 1 of the following:

• Histologically confirmed disease
• Pathologically documented disease and clinical course consistent with prostate cancer
• Castrate levels of testosterone with progressive disease by at least 1 of the following parameters:

• 2 consecutively rising prostate-specific antigen levels, separated by at least 1 week, with at least 1 measurement that is 50% above the nadir reached after the last therapeutic maneuver (must be at least 5 ng/mL)
• At least 1 new metastatic deposit on technetium Tc 99 bone scintigraphy
• Progression of soft-tissue metastases by imaging or palpation, as indicated by:

• Development of new area of malignant disease
• At least 20% increase in sum of the longest dimension of target lesions
• Serum testosterone less than 50 ng/dL if no prior surgical castration

• Luteinizing hormone-releasing hormone therapy must continue
• HLA-A2 positive
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Lymphocyte count at least 500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 1.5 mg/dL
• AST and ALT less than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN OR
• Hepatic alkaline phosphatase fraction less than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 40 mL/min
• Proteinuria grade 0-1 OR
• Protein less than 1,000 mg by 24-hour urine collection
• No hematuria
• No abnormal sediment unless non-renal

Cardiovascular

• No unstable or newly diagnosed angina pectoris
• No myocardial infarction within the past 6 months
• No New York Heart Association class II-IV congestive heart failure
• No concurrent clinically significant cardiomyopathy requiring treatment

Immunologic

• No prior allergy or untoward reaction to vaccinia virus vaccination
• No altered immune function, including:

• Eczema
• Atopic dermatitis
• HIV
• Autoimmune disease

• Autoimmune neutropenia
• Thrombocytopenia
• Hemolytic anemia
• Systemic lupus erythematosus
• Sjogren's syndrome
• Scleroderma
• Myasthenia gravis
• Goodpasture syndrome
• Addison's disease
• Hashimoto's thyroiditis
• Active Graves' disease
• Multiple sclerosis
• No extensive psoriasis, severe acneiform rash, impetigo, varicella zoster, burns, or other traumatic or pruritic skin condition
• No known allergy to eggs

Other

• No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the bladder
• No other life-threatening or serious illness
• No unhealed surgical scars
• No household or close physical contact with persons with any of the following conditions during or for 2 weeks after study treatment:

• Eczema or eczematoid skin disorders
• Acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Pregnant or nursing women
• Children under 5 years of age
• Immunodeficient or immunosuppressed (including HIV positive) individuals
• No history of seizures or encephalitis

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior taxanes for metastatic prostate cancer

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior flutamide
• At least 6 weeks since prior bicalutamide or nilutamide
• No concurrent steroids except topical steroids, inhaled steroids for mild or moderate asthma, or decadron as premedication for chemotherapy

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• No prior splenectomy

Other

• Recovered from prior therapy