Protocol Number: 00-C-0154

Title:

A Randomized Phase II Study of a PSA-Based Vaccine in Patients with Localized Prostate Cancer Receiving Standard Radiotherapy

Number:

00-C-0154

Summary:

This study will test the ability of an experimental vaccine to prevent the spread of localized prostate cancer following radiation therapy. The vaccine is intended to stimulate immune cells called lymphocytes to target and attack cells containing a protein called prostate specific antigen, or PSA. It is composed of the following five parts: rV-PSA - vaccinia virus plus human DNA that produces PSA (prostate specific antigen); rV-B7.1 - vaccinia virus plus human DNA that produces B7.1 (a protein that helps activate immune cells); rF-PSA - fowlpox virus plus human DNA that produces PSA; and GM-CSF and IL-2 - two drugs that boost the immune system.

Patients age 18 years and older with prostate cancer confined to the prostate who have been vaccinated against smallpox (vaccinia virus vaccine) and who do not have a history of allergy to eggs may participate in this study. Candidates will be screened for eligibility with a complete medical history and physical examination, skin tests (similar to those for allergies or tuberculosis) to assess immune function and blood tests.

Participants will be randomly assigned to one of two treatment groups: one will receive standard radiation therapy, but no vaccine; the other will receive standard radiation therapy plus the experimental vaccine. Patients in both groups may receive hormone therapy, if indicated.

Patients in the vaccine group will receive up to eight vaccinations in 28-day treatment cycles, as follows: GM-CSF on days 1 through 4; IL-2 days 8 through 12; rV-PSA and rV-B7.1 day 2 of the first cycle only; and rF-PSA (booster shots) every 28 days, beginning day 2 of the second cycle (i.e., days 30, 58, 86, etc.). The vaccinations are injected under the skin of the upper arm. Treatment will continue for eight cycles unless serious side effects develop, PSA levels rise significantly, or the doctors feel there is no reason to continue. Radiation therapy will be started about 3 months after enrollment in the study. Patients will have 15 cc (one tablespoon) of blood drawn once a week for the first month and then 60 cc (4 tablespoons) once every 4 weeks. After treatment ends, patients will have follow-up examinations and blood tests every 3 months for the first 2 years and then every 6 months until the doctors determine follow-up is no longer needed or the cancer returns.

All patients will have HLA tissue typing at the beginning of the study. Only those who are HLA-A2 positive can go on this study. This will enable studies of the immune response that can be done only with this tissue type. These include blood collection (60 cc) every 4 weeks and a procedure called lymphapheresis for collecting white blood cells. In this procedure, whole blood is collected through a needle in an arm vein, similar to donating a unit of blood. The blood flows through a machine that separates it into its components. The white cells are removed, and the red cells, platelets and plasma are returned to the body, either through the same needle used to draw the blood or through a second needle in the other arm.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male

Referral Letter Required: No

Population Exclusion(s): Female

Eligibility Criteria:

INCLUSION CRITERIA:

Patients with histologically confirmed diagnosis of adenocarcinoma of the prostate who are candidates for definitive radiotherapy, who have not had local therapy but who agree to be treated with radiotherapy (external beam therapy alone or in combination with brachytherapy).

Patients must be HLA-A2 positive for cohorts A and B. At least 9 patients must be HLA-A2 positive in cohort C.

Zubrod (ECOG) performance 0-1.

Age greater than or equal to 18 years.

Concurrent hormonal therapy will be allowed.

Patients must have received prior vaccinia (for smallpox immunization). For patients less than 30 years of age, physician certification of prior smallpox immunization is required. For patients greater than or equal to age 30, patient recollection and appropriate vaccination-site scar is sufficient evidence. There must be no history of allergy or untoward reaction to prior vaccination with vaccinia virus.

Absolute lymphocyte count greater than or equal to 600/mm(3); platelets greater than or equal to 100,000/mm(3); hemoglobin greater than or equal to 8.0 grams/dl.

The initial urine analysis for eligibility should be less than or equal to grade 1 proteinuria, grade 0 hematuria and no abnormal sediment. Any positive protein, including trace values, should be evaluated by a 24-hour urine less than or equal to 1 gram per 24 hours. Any other abnormalities in the sediment or the presence of hematuria should be evaluated by a nephrologist for evidence of underlying renal pathology. Patients may be eligible if the underlying cause of the abnormality is determined to be non-renal.

Serum bilirubin less than or equal to 1.6 mg/dl, AST and ALT less than or equal to 4 times normal; serum creatinine less than or equal to 1.5 mg/dl or a creatinine clearance of greater than 60 ml/min.

Patients must understand and sign informed consent that explains the neoplastic nature of his disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.

EXCLUSION CRITERIA:

Patients should have no evidence of being immunocompromised as listed below:

They should have no reactive HIV testing;

They should not have any other diagnosis of altered immune function, autoimmune disease (autoimmune neutropenia, thrombocytopenia, or hemolytic anemia; systemic lupus erythematosus, Sjogren syndrome, or scleroderma; myasthenia gravis; Goodpasture syndrome; Addison's disease, Hashimoto's thyroiditis, or active Graves' disease).

They should not have prior radiation therapy greater than 50% of nodal groups;

They should not have had a prior splenectomy;

They should not be using glucocorticoids (including glucocorticoids for brachytherapy).

The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least two weeks after vaccination, their close household contacts: Persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne or other open rashes or wound) until condition resolves; Pregnant or nursing women; Children under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy) , including HIV infection. Close household contacts are those who share housing or have close physical contact.

Other serious intercurrent illness. Patients with active infections requiring antibiotic treatment (including chronic suppressive therapy) are not eligible until the infection has cleared and the antibiotics have been stopped for at least three days.

History of other malignant process (excluding squamous cell or basal cell carcinoma of the skin), unless that previous tumor was treated with curative intent and the patient has been in remission for at least three years.

Patients with a history of seizures, encephalitis, or multiple sclerosis are not eligible.

Patients with known allergy to eggs are not eligible.

Patients should not have any cardiac disease, pulmonary disease, autoimmune disease, renal disease or hepatic dysfunction that may be exacerbated by IL-2.

Special Instructions: Currently Not Provided

Keywords:

Immunotherapy

Radiation

Immunology

Prostvac

Recruitment Keywords:

Prostate Cancer

Conditions:

Prostate Cancer

Prostate Neoplasm

Investigational Drug(s):

rV-PSA

rF-PSA

rV-B7.1

Investigational Device(s):

None

Contacts:

CSSC
Clinical Studies Support Center/NCI
164 Rollins Avenue
2nd FLoor
Rockville, MD 20852
Phone: (888) 624-1937
Fax: (301) 881-8239

Electronic Address: ncicssc@mail.nih.gov

Citations:

Recombinant vaccinia-PSA (PROSTVAC) can induce a prostate-specific immune response in androgen-modulated human prostate cancer

Expression of human prostate-specific antigen (PSA) in a mouse tumor cell line reduces tumorigenicity and elicits PSA-specific cytotoxic T lymphoctyes

Prognostic significance of changes in prostate specific markers after endocrine treatment of stage D2 prostatic cancer

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