Sequential Vaccinations in Prostate Cancer Patients

Inclusion Criteria

• •Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), or National Naval Medical Center (NNMC) prior to starting this study.
• •If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• •Patients must have androgen insensitive metastatic prostate cancer.
• •Progression must be documented by at least one of the following parameters:
• •1. All patients must have received standard of care (hormonal) treatment before entering the trial.
• •2. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.
• •3. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible for this Phase I trial; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.
• •i. Two consecutively rising prostatic specific antigen (PSA) levels, separated by at least 1 week, with at least one measurement that is 50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and
• •ii. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or
• •iii. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).
• •Patients must have a life expectancy of more than 6 months.
• •Patients must have a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) criteria.
• •Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).
• •2. Hepatic function: Bilirubin less than 1.5 mg/dl,
• •aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal.
• •3. Patients must be test negative for human immunodeficiency virus (HIV), Hepatitis B and C.
• •Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
• •Patients must be willing to travel to the National Institutes of Health (NIH) for follow-up visits.
• •Patients must be greater than or equal to 18 years of age.
• •All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the Centers for Disease Control (CDC), prior vaccinia vaccination as a safety precaution is no longer required.
• •Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.
• •Patients must not have received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan.
• •Patients must not have received prior PSA vaccine therapy.
• •Patients will tested for human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2). This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the NIH Clinical Center. These patients must have measurable disease on computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.
• •The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.
• •Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), or National Naval Medical Center (NNMC) prior to starting this study. If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• •1. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.
• •2. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.
• •i. Two consecutively rising PSA levels, separated by at least 1 week, with at least one measurement that is 50% above the
• •nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and
• •ii. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or
• •iii. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).
• •Patients must have a life expectancy of more than 6 months.
• •Patients must have a performance status of 0 to 2 according to the ECOG criteria.
• •Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).
• •Hematological eligibility parameters (within 16 days of starting therapy):
• •Granulocyte count greater than or equal to 1,500/mm\^3
• •Platelet count greater than or equal to 100,000/mm\^3
• •Lymphocyte count greater than or equal to 500/mm\^3
• •Hgb greater than or equal to 10 Gm/dL
• •Biochemical eligibility parameters (within 16 days of starting therapy):
• •1. A 24-hour urine collection for baseline to measure creatinine clearance (CrCl), protein and electrolytes.
• •CrCl greater than 60
• •proteinuria less than 1000 milligrams per 24 hours, less than or equal to Grade 1 (NCI-Common Toxicity Criteria (CTC) version 2.0) proteinuria, Grade 0 hematuria, and no abnormal sediment.
• •Grade 0 creatinine.
• •Patients must have serum creatinine within normal limits.
• •2. Hepatic function: Bilirubin less than 1.5 mg/dl,
• •AST and ALT less than 2.5 times upper limit of normal.
• •3. Patients must test negative for HIV, Hepatitis B and C.
• •Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
• •Patients must be willing to travel to the NIH for follow-up visits.
• •Patients must be greater than or equal to 18 years of age.
• •All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the CDC, prior vaccinia vaccination as a safety precaution is no longer required.
• •Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.
• •Patients have not received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan.
• •Patients have not received prior PSA vaccine therapy.
• •All patients will tested for HLA-A2. Patients must be HLA-A2+. This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the National Institutes of Health (NIH) Clinical Center. These patients must have measurable disease on computed tomography (CT), magnetic resonance imaging (MRI), or bone scan.
• •The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.