Overview

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

Status:
Completed
Trial end date:
2010-10-01
Target enrollment:
0
Participant gender:
Male
Summary
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. 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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Bicalutamide
Goserelin
Metronidazole
Sargramostim
Vaccines
Criteria
Inclusion Criteria:

- Patients with histologically proven prostate cancer and tumors limited to the prostate
(including seminal vesical involvement, provided all visible disease was surgically
removed) that have completed local therapy and have an elevated PSA after surgery or
rising PSA after radiation therapy, as defined below; patients with lymph node
involvement (D1) are not eligible

- Histologically confirmed diagnosis of prostate cancer

- Previous treatment with definitive surgery or radiation therapy or both

- No evidence of metastatic disease on physical exam, CT (MRI), and bone scan within 4
weeks prior to randomization

- Prior neoadjuvant/adjuvant hormonal or chemotherapy is allowed if it was last used >=
1 year prior to enrollment (no prior vaccine/immunotherapy for prostate cancer will be
allowed)

- No therapy modulating testosterone levels (such as leuteinizing-hormone
releasing-hormone agonists/antagonists and antiandrogens) is permitted within 1 year
prior to enrollment; agents such as 5-reductase inhibitors, ketoconazole, megestrol
acetate, systemic steroids, and herbal products are not permitted at any time during
the period that the PSA values are being collected

- Hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150
ng/dL at the time of enrollment within 4 weeks prior to randomization

- There must be one PSA measurement (referred to as the baseline PSA) obtained within
one week prior to registration; the baseline PSA value must be greater than 0.4 ng/mL
(after prostatectomy) or greater than 1.5 ng/mL (after radiation therapy)

- All patients must have evidence of biochemical progression as determined by 3 PSA
measurements (PSA1, PSA2, PSA3), each higher than the previous value, each obtained at
least 4 weeks apart from the others with the most recent one (PSA3) being the baseline
PSA; all of these PSA values must be obtained at the same reference lab; the earliest
(PSA1) must be done within 6 months prior to registration.

- PSA doubling time (PSADT) must be less than 12 months, calculated using the following
formula:

PSADT in days = (0.693 (t))/(In (PSA3) - In (PSA2)) Where t = the number of days between
PSA3 and PSA2 In = the natural log PSADT in months = PSADT in days divided by 30.4375

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1

- Leukocytes >= 3000/mm^³

- Granulocytes >= 1500/mm^3

- Platelet count >= 100,000/mm^3

- Serum creatinine within normal institutional limits or creatinine clearance >= 60
mL/min for patients with creatinine levels above institutional normal (a calculated
clearance may be used); an initial urine analysis will be required with grade 0
proteinuria and no abnormal sediment; for any positive protein a 24 hour urine should
be less than 1,000 mg per 24 hours and no indication of chronic renal disease

- Serum total bilirubin, and alkaline phosphatase within normal institutional limits

- SGOT (AST) and SGPT (ALT) =< 2.5 x institutional upper limit of normal

- Patients cannot have evidence of immunosuppression:

- Patients must be human immunodeficiency virus sero-negative due to the potential
for severe reactions to vaccinia and the need for an intact immune system to
respond to the immunization

- Patients must not have active autoimmune diseases such as Addison's disease,
Hashimoto's thyroiditis, systemic lupus erythematous, Sjogren syndrome,
scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease;
patients with a history of autoimmunity that has required systemic
immunosuppressive therapy or has impaired organ function including CNS, heart,
lungs, kidneys, skin, and GI tract are ineligible; patients receiving replacement
thyroid hormone would be eligible

- No concurrent use of systemic steroids, except for local (topical, nasal, or
inhaled) steroid use; steroid eye drops are contraindicated for at least 2 weeks
before vaccinia vaccination and at least 4 weeks post vaccinia vaccination

- Patients must be hepatitis B and hepatitis C negative

- Patients must have a normal PT/INR within 4 weeks prior to randomization

- Patients must not be receiving any other investigational agents or receiving
concurrent anticancer therapy

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements; because of the recently recognized risk of cardiac inflammation
after vaccinia, patients with clinically significant cardiomyopathy are excluded;
patients must have recovered from any intercurrent illness and any acute toxicity
related to prior therapy (i.e., surgery and/or radiation)

- Patients must use a safe and effective method of contraception to prevent virus
transmission; the potential risk to spermatogenesis and fetal development after
paternal immunization with this vaccine is not known; patients must agree to avoid
fathering a child and use a latex barrier with adequate contraception prior to study
entry and for at least 4 months following the last vaccine injection

- All sites of disease must be evaluated within 4 weeks prior to registration

- Patients with significant allergy or hypersensitivity to eggs should be excluded;
patients must not have a history of allergy or untoward reaction to prior vaccination
with vaccinia virus or to any component of the vaccinia vaccine regimen

- Patients must not have active eczema, a history of eczema, atopic dermatitis, or
Darier.s disease; other acute, chronic, or exfoliative skin conditions (e.g., burns,
impetigo, varicella zoster, severe acne, contact dermatitis, psoriasis, herpes or
other open rashes or wounds

- Patients must be able to avoid close contact with those who share housing or have
close physical contact for at least three weeks after recombinant vaccinia vaccination
with persons at increased risk including those with active or a history of eczema or
atopic dermatitis, or Darier"s disease; those with other acute, chronic or exfoliative
skin conditions (e.g., burns, impetigo, varicella zoster, severe acne, contact
dermatitis, psoriasis, herpes 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), which includes
those infected with HIV until the condition resolves