Phase I Trial of In Situ Gene Therapy for Locally Recurrent Prostate Cancer Following Radiation Therapy Failure Using Sodium/Iodide Symporter and Radioiodine


Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

OBJECTIVES: Primary - To determine the safety and tolerance of Ad5CMV-NIS administered intraprostatically followed by radioiodine treatment in patients with locally recurrent adenocarcinoma of the prostate following external beam radiotherapy. - To determine the maximum tolerated dose of Ad5CMV-NIS in these patients. Secondary - To evaluate the PSA response rates, duration, and time to PSA progression in these patients. - To evaluate the immune response to Ad5CMV-NIS. OUTLINE: This is a dose-escalation study of Ad5CMV-NIS. Patients receive intraprostate Ad5CMV-NIS, via transperineal injection under anesthesia, on day 1. They receive dosimetry oral iodine I 123 on day 4 and undergo image studies periodically for the next 24 hours for measurement of radioiodine uptake. Patients receive therapeutic oral iodine I 131 on day 5. All patients with intact thyroid glands (i.e., not previously surgically removed or ablated) receive TSH suppressive doses of oral liothyronine sodium 3 times daily for 10 days prior and for 15 days post administration of iodine I 123. Blood samples are collected periodically for measurement of PSA, fT4, and TSH; and peripheral blood cells are monitored for evidence of virus DNA via quantitative reverse-transcriptase-PCR. After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 8 years. A transrectal tumor biopsy is to be performed at 3 months and 1 year post-treatment.

Who is eligible to participate?

DISEASE CHARACTERISTICS: - Histologically confirmed recurrent adenocarcinoma of the prostate within the past year - No transitional cell, small cell, or squamous cell carcinoma of the prostate - Local recurrence - Disease recurred ≥ 18 months after completion of prior external beam radiotherapy (EBRT) for stage T1-T2b, N0/X, M0 disease - Biochemical failure as defined by the Phoenix definition (rise in PSA by 2 ng/mL or more above the nadir PSA) - PSA ≥ 0.3 ng/mL to < 20 ng/mL measured within the past 30 days - Pre-EBRT PSA < 50 ng/mL - Prior locally recurrent hormone-refractory disease allowed - American Urologic Association Obstructive Symptom Index Score ≤ 24 - No known standard therapy that is potentially curative or definitely capable of extending life expectancy - No evidence of or history of metastatic adenocarcinoma of the prostate - Negative radiographic metastatic work-up including whole-body radionuclide bone scan, CT and/or MR scan of the pelvis and abdomen, and chest x-ray - Patients with suspicious areas on conventional imaging studies are eligible provided they are biopsy negative - No known CNS metastases - No prostate size > 140 cc PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Life expectancy ≥ 12 weeks - ANC ≥ 1,500/μL - Platelet count ≥ 100,000/μL - Hemoglobin ≥ 8.5 g/dL - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - INR ≤ 1.4 times ULN - Creatinine ≤ 1.5 times ULN - Thyroid-stimulating hormone 0.3-5.0 uIU/mL and free thyroxine 0.8-1.87 ng/dL - Willing to provide biologic specimens and participate in imaging studies as required - Willing to maintain a low-iodine diet for 12 days - Starting 7 days prior to study virus injection continuing until after the iodine I 131 radioiodine therapy on day 5 - No more than 1 of the following renal/genitourinary toxicities: - Bladder spasms - Dysuria (painful urination) - Genitourinary fistula - Hemoglobinuria - Incontinence - Operative injury to bladder and/or ureter - Proteinuria - Renal failure - Uretal obstruction - Urinary frequency/urgency - Urinary retention - Urine color change (not related to other dietary or physiologic cause [e.g., bilirubin, concentrated urine, or hematuria]) - Other renal/genitourinary toxicities - No urinary tract infection within 72 hours prior to registration - No pubic arch interference study demonstrating unacceptable prostate access by the transperineal approach - No absence of rectum or other anatomic features that would preclude transperineal needle insertion into the prostate - No coagulopathy that contraindicates transperineal and intraprostatic needle insertion - No other cancer within the past 2 years, except for squamous cell and basal cell skin cancers - No uncontrolled infection or fever > 100°F - No known cardiac disease - No seizure disorder - No documented history of HIV positivity or other acquired immunodeficiency disorder or congenital immunodeficiency disorder PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Recovered from acute, reversible effects of prior chemotherapy - Androgen-deprivation therapy (if applicable) initiated more than 3 months prior to registration - Patients who have undergone bilateral orchiectomy are eligible if they meet all other criteria - At least 6 weeks since prior bicalutamide, nilutamide, or oral or intravenous iodinated contrast - At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas), immunotherapy, biologic therapy, or other experimental drugs - At least 4 weeks since prior and no concurrent anti-androgens (e.g., flutamide, estrogens, ketoconazole, PC-SPES, finasteride, or megestrol acetate) - At least 2 weeks since prior and no concurrent exogenous corticosteroids - Patients clinically proven to require maintenance steroids allowed provided there has been no change in their dose within the past 6 weeks - No antibiotic therapy within the past 72 hours - No prior organ transplantation - No prior salvage prostatectomy or brachytherapy - No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational - No concurrent prophylactic use of colony-stimulating factors - No concurrent enrollment in any other study involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, gene therapy) whether for symptom control or therapeutic intent

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