Vaccine Therapy and GM-CSF in Treating Patients With Prostate Cancer That Progressed After Surgery and/or Radiation Therapy

Condition(s) targeted: Prostate Cancer

Intervention: bicalutamide (Drug); fowlpox-PSA-TRICOM vaccine (Drug); goserelin (Drug); sargramostim (Drug); vaccinia-PSA-TRICOM vaccine (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Eastern Cooperative Oncology Group

Official(s) and/or principal investigator(s):
Robert S. DiPaola, MD, Study Chair, Affiliation: Cancer Institute of New Jersey
David Jarrard, MD, Affiliation: University of Wisconsin, Madison

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.

Official title: A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer

Study design: Treatment, Open Label

Primary outcome:

Proportion of patients free of PSA progression before 6 months (prior to the start of androgen ablation)

Characterization of PSA velocity

PSA response on vaccine

Time to androgen independent progression

Secondary outcome:

PSA response on vaccine

Proportion of patients who demonstrate a T-cell immune response

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

Cancer Care and Hematology Specialists of Chicagoland - Niles, Niles, Illinois 60714, United States

Hematology and Oncology Associates, Chicago, Illinois 60611, United States

Hematology Oncology Associates - Skokie, Skokie, Illinois 60076, United States

Hematology/Oncology of the North Shore at Gross Point Medical Center, Skokie, Illinois 60076, United States

Mercy Hospital and Medical Center, Chicago, Illinois 60616, United States

Midwest Center for Hematology/Oncology, Joliet, Illinois 60432, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States

Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States

McCreery Cancer Center at Ottumwa Regional, Ottumwa, Iowa 52501, United States

Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2006
Last updated: May 23, 2008