Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

OBJECTIVES:

Primary

• Determine the 6-month biochemical prostate-specific antigen (PSA) progression in patients with PSA progression after local therapy for early prostate cancer treated with vaccine therapy comprising vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine combined with sargramostim (GM-CSF).

• Determine the pre- and post-treatment changes in PSA slope/velocity in these patients.

Secondary

• Determine the percentage of patients treated with this regimen who experience a ≥ 50% PSA decline at 4 weeks.

• Determine the tolerability and toxicity of this regimen in these patients.

• Compare the effect of GM-CSF on PSA at day 4 after treatment vs at day 15 after treatment in these patients.

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 weeks 1-4. Beginning in week 5, 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 3 courses (weeks 5-16). Beginning in week 17, 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 receive 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.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 6 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer

• Tumor limited to the prostate

• Seminal vesical involvement allowed provided all visible disease has been surgically removed

• No lymph node involvement

• Hormone-sensitive disease

• Testosterone level > 150 ng/dL

• Evidence of prostate-specific antigen (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, determined by a reference PSA value* followed by 2 rising PSA values* 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 NOTE: *At least 3 PSA values must have been obtained at the same reference laboratory before the baseline PSA value is obtained

• No metastatic disease by physical exam, CT scan, MRI, or bone scan within the past 4 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3

• Granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal

• Bilirubin normal

• Alkaline phosphatase normal

• Hepatitis B surface antigen negative

• Hepatitis C antibody negative

• PT/INR normal

Renal

• No proteinuria or abnormal sediment by urine analysis OR

• 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

Cardiovascular

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No clinically significant cardiomyopathy

Immunologic

• No history of autoimmune disease that has required systemic immunosuppressive therapy or has impaired CNS, heart, lung, kidney, skin, or gastrointestinal tract function

• No history of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the study vaccinia vaccine

• No significant allergy or hypersensitivity to eggs

• HIV negative

• 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

• Active Graves' disease

• No history of or active eczema

• No ongoing, active infection

• No atopic dermatitis

• No Darier's disease

• No 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

• No other evidence of immunosuppression

Other

• Fertile patients must use effective contraception during and for at least 4 months after completion of study treatment

• No psychiatric illness or social situation that would preclude study compliance

• Recovered from any other illness

• No other concurrent uncontrolled 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

• Individuals with active atopic dermatitis

• Individuals with 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior vaccine therapy or immunotherapy for prostate cancer

Chemotherapy

• At least 1 year since prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

• At least 1 year since prior neoadjuvant or adjuvant hormonal therapy

• More than 1 year since prior testosterone level-modulating therapy, including either of the following:

• Luteinizing hormone-releasing hormone agonists or antagonists

• Antiandrogens

• No 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

• Concurrent thyroid hormone-replacement therapy allowed

• None of the following agents are allowed during the period in which the PSA levels are determined:

• 5α-reductase inhibitors

• Ketoconazole

• Megestrol

• Systemic steroids

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy

• No herbal products during the period in which the PSA levels are determined

• No other concurrent investigational agents

• No other concurrent anticancer therapy

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Robert S. DiPaola

Study Chair

David Jarrard

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00108732
Information obtained from ClinicalTrials.gov on December 14, 2011

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