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

NCT ID: NCT00788307

Last Updated: 2023-04-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-03
• Study Completion Date: 2018-02-07

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental Arm

Group Type: EXPERIMENTAL

Ad5-CMV-NIS

Intervention Type: BIOLOGICAL

liothyronine sodium

Intervention Type: DRUG

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

laboratory biomarker analysis

Intervention Type: OTHER

iodine I 131

Intervention Type: RADIATION

Interventions

Ad5-CMV-NIS

Intervention Type: BIOLOGICAL

liothyronine sodium

Intervention Type: DRUG

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

laboratory biomarker analysis

Intervention Type: OTHER

iodine I 131

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian J. Davis, M.D.

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC0252

Identifier Type: OTHER

Identifier Source: secondary_id

06-009392

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-01195

Identifier Type: OTHER

Identifier Source: secondary_id

MC0252

Identifier Type: -

Identifier Source: org_study_id