A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
Background:
Objectives:
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer.
Eligibility:
Design:
Background:
Objectives (Primary):
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone.
Eligibility:
Design:
-Flutamide will be administered at a dose of 250 mg PO (by mouth) tid (three times a day) every day in both arms A and B.
rV-PSATRICOM will be administered s.c. (subcutaneous) on day 1 in Arm B.
rF-PSATRICOM will be administered s.c. on day 29 & every 4 weeks in Arm B.
A. Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the: National Institutes of Health (NIH) Clinical Center prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
B. Must have non-metastatic androgen insensitive prostate cancer with a rising PSA (prostatic specific antigen) with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.
C. Life expectancy greater than or equal to 6 months.
D. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
F. Hematological eligibility parameters:
G. Biochemical eligibility parameters (within 16 days of starting therapy)
-Hepatic function: Bilirubin less than or equal to 1.5 mg/dl, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
H. No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
I. Willing to travel to the NIH for follow-up visits.
J. 18 years of age or greater.
K. Able to understand and sign informed consent.
L. Must agree to use effective birth control (such as a condom) or abstinence during and for a period of 4 months after the last vaccination therapy. Patients must be willing to remain on chemical castration therapy, unless they have had surgical castration.
M. Patients must have recovered from acute toxicities related to prior therapy or surgery.
N. Parameters for assessment of baseline renal function:
Serum creatinine less than or equal to 1.5 times the upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.
EXCLUSION CRITERIA:
A. Patients should have no evidence of being immunocompromised as listed below.
B. Patients who test positive for active Hepatitis B or Hepatitis C infection.
C. Patients should have no autoimmune diseases that have required treatment such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, active Grave's disease.
D. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.
E. Do not administer the recombinant vaccinia vaccine if the recipient, or for at least three weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact) are: 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 wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV (human immunodeficiency virus) infection.
F. Serious intercurrent medical illness (e.g., one that requires treatment) which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
G. Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible.
H. Patients with a history of congestive heart failure or who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
I. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.
J. Concurrent chemotherapy.
K. No known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis.
L. Patients with a serious hypersensitivity reaction to egg products are not eligible.
M. Prior splenectomy.
N. Patients who have received prior flutamide therapy in the last year. (Patients treated with flutamide in the neoadjuvant or adjuvant setting or those previously treated with flutamide who did not have a rising PSA on treatment would be allowed to enroll on the protocol.)