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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

Phase 1
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

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



- 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

- 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

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.

Inclusion Criteria


- Histologically confirmed recurrent adenocarcinoma of the prostate within the past

- 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

- 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

- No other cancer within the past 2 years, except for squamous cell and basal cell skin

- 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


- See Disease Characteristics

- Recovered from acute, reversible effects of prior chemotherapy

- Androgen-deprivation therapy (if applicable) initiated more than 3 months prior to

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of toxicity incidents by NCI CTCAE v3.0 criteria

Safety Issue:


Principal Investigator

Brian J. Davis, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage I prostate cancer
  • stage II prostate cancer
  • Prostatic Neoplasms



Mayo Clinic Rochester, Minnesota  55905