A Phase I Feasibility Study of an Intraprostatic PSA-Based Vaccine in Men With Prostate Cancer With Local Failure Following Radiotherapy or Cryotherapy or Clinical Progression on Androgen Deprivation Therapy in the Absence of Local Definitive Therapy

Completed · Phase 1

Conditions studied: Prostatic Neoplasms

In brief

Background: * Pox viral vectors can induce a PSA-specific T-cell responses and clinical responses in patients with advanced prostate cancer. * Intratumoral vaccines of recombinant fowlpox vectors appear to be more potent in inducing antitumor effects than the s.c. route of administration, especially when the recombinant rF-vector given intratumorally is preceded by a rV-recombinant given s.c. This may be due to: * Making the tumor cell an antigen presenting cell via upregulation of both antigen (signal 1) and costimulatory molecules (signal 2). * Making the tumor cell more susceptible to killing via upregulation of ICAM. * The increased expression of perforin in peptide-specific T cells that came into contact with the TRICOM-infected targets. * Potentially allowing the immune system to select for other tumor encoded antigens to generate a polyvalent immune response. Objectives: * 1: Safety and feasibility of an intraprostatic vaccine strategy. * 2: To assess the change in PSA-specific T-cell response as measured by ELISPOT assay. * 2: To evaluate T-cell infiltration histologically in patients who have pre- and post-vaccine prostate biopsies. Eligibility: * Must have either a) biopsy proven, locally recurrent prostate cancer following local radiation as defined by the ASTRO consensus criteria as 3 consecutively rising PSA levels or b) have refused or not be candidates for local definitive therapy (surgery or radiation therapy) and have clinically progressive disease on androgen deprivation therapy (eg. three increases in PSA over nadir, separated by at least one week). For patients with previous RT, the biopsy confirming local recurrence must be done at least 18 months after the completion of RT. * Since this may also generate a systemic immune response, patients with minimal extraprostatic disease may be enrolled. * Hepatic function: Bilirubin \< 1.5 mg/dl, AST and ALT\< 2.5 times upper limit of normal Design: * Dose escalation Phase I design. Each cohort will consist of 3-6 patients, with cohorts 4 \& 5 restricted to include only HLA-A2 + patients; maximum accrual is 30 * Patients in all cohorts receive initial priming with rV- PSA(L155)/TRICOM and rF-GM-CSF s.c. * The first two cohorts utilize a booster intraprostatic with dose escalation of rF-PSA(L155)/TRICOM. * Third and fourth cohorts add dose escalations of rF-GM-CSF along with the highest dose of rF-PSA(L155)/TRICOM * Last (5th) cohort u...

Key facts

Study ID: NCT00096551
Run by: National Cancer Institute (NCI)
People needed: 21
Starts: 2004-11-01
Expected to finish: 2011-07-25
Last updated by the study team: 2017-07-02

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may not qualify if…

A. Patients should have no evidence of being immunocompromised as listed below.
Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects.
Active autoimmune diseases such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome active Grave's disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
Hepatitis B or C positivity.
Concurrent use of systemic steroids, except for physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Steroid eye drops are contraindicated for at least 2 weeks prior vaccinia vaccination and at least 4 weeks post vaccinia vaccination.
B. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.
C. Must be able to avoid close household contact (close household contacts are those who share housing or have close physical contact) for at least three weeks after recombinant vaccinia vaccination with 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 infection.
D. Serious intercurrent medical illness 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.
E. 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.
F. Patients who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
G. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.
H. Concurrent chemotherapy.
I. Clinically active brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis.
J. Serious hypersensitivity reaction to egg products.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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