Phase I Trial of In Situ Gene Therapy for Locally Recurrent Prostate Cancer Following Radiation Therapy Failure Using Sodium/Iodide Symporter and Radioiodine
Trial status: Open for Enrollment
Why is this study being done?
- 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.
- 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?
- 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
- 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
- Operative injury to bladder and/or ureter
- 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