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

Sponsor

Mayo Clinic (Other)

Overall Status

Terminated

CT.gov ID

NCT00788307

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

111.1

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: Ad5-CMV-NIS Drug: liothyronine sodium Genetic: reverse transcriptase-polymerase chain reaction Other: laboratory biomarker analysis Radiation: iodine I 131	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 3, 2008

Actual Primary Completion Date :

Feb 7, 2018

Actual Study Completion Date :

Feb 7, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Experimental Arm

Biological: Ad5-CMV-NIS

Drug: liothyronine sodium

Genetic: reverse transcriptase-polymerase chain reaction

Other: laboratory biomarker analysis

Radiation: iodine I 131

Outcome Measures

Primary Outcome Measures

Number of toxicity incidents by NCI CTCAE v3.0 criteria [3 years]

Secondary Outcome Measures

Time to PSA progression [3 years]
Survival [3 years]
Incidence and duration of PSA response [3 years]
Duration of PSA control [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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