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

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

Status
Terminated
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00788307
Enrollment
8
Registered
2008-11-10
Start date
2008-11-03
Completion date
2018-02-07
Last updated
2023-04-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate, recurrent prostate cancer, stage I prostate cancer, stage II prostate cancer

Brief summary

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

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.

Interventions

BIOLOGICALAd5-CMV-NIS
GENETICreverse transcriptase-polymerase chain reaction
OTHERlaboratory biomarker analysis
RADIATIONiodine I 131

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Mayo Clinic
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No

Inclusion criteria

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

Design outcomes

Primary

MeasureTime frame
Number of toxicity incidents by NCI CTCAE v3.0 criteria3 years

Secondary

MeasureTime frame
Time to PSA progression3 years
Survival3 years
Incidence and duration of PSA response3 years
Duration of PSA control3 years

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026