Gene Therapy and Radioactive Iodine in Treating Patients With Locally Recurrent Prostate Cancer That Did Not Respond to External-Beam Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: Radioactive drugs, such as radioactive iodine, may carry radiation directly to tumor cells and not harm normal cells. Placing a gene called Ad5CMV-NIS in prostate cancer cells may help the prostate cells take in more radioactive iodine and thus kill the cancer cells. Drugs, such as liothyronine sodium, may protect the thyroid from the side effects of radioactive iodine. PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy given together with radioactive iodine in treating patients with locally recurrent prostate cancer that did not respond to external-beam radiation therapy.

Detailed Description
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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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Ad5-CMV-NIS
* Drug: liothyronine sodium
* Genetic: reverse transcriptase-polymerase chain reaction
* Other: laboratory biomarker analysis
* Radiation: iodine I 131


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br> | Biological: Ad5-CMV-NIS<br> <br> Drug: liothyronine sodium<br> <br> Genetic: reverse transcriptase-polymerase chain reaction<br> <br> Other: laboratory biomarker analysis<br> <br> Radiation: iodine I 131<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of toxicity incidents by NCI CTCAE v3.0 criteria |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to PSA progression |  | 3 years | 
| Survival |  | 3 years | 
| Incidence and duration of PSA response |  | 3 years | 
| Duration of PSA control |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, recurrent prostate cancer, stage I prostate cancer, stage II prostate cancer