A Phase I Study of In-Situ, Neoadjuvant, Pre-Radical Prostatectomy RTVP-1 Gene Therapy in Patients With Locally Advanced Adenocarcinoma of the Prostate (SPORE)
18 Years
N/A
Male
Prostatic Neoplasms
Trial Information
A Phase I Study of In-Situ, Neoadjuvant, Pre-Radical Prostatectomy RTVP-1 Gene Therapy in Patients With Locally Advanced Adenocarcinoma of the Prostate (SPORE)
The population selected for this study includes patients with locally advanced and/or poorly
differentiated tumors. These patients have an unacceptably high failure rate when treated
by radical prostatectomy alone (over 50% fail within 5 years). The pattern of failure
varies. While some patients present with a local recurrence, many have both a local
recurrence and distant metastases, or just distant metastases. It is reasonable to assume
that many, if not most of these patients, actually harbor micrometastases, present but
undiagnosed clinically, at the time of their radical prostatectomy. Our hypothesis is that
the cytotoxic, proapoptotic, antiangiogenic and immune stimulatory activities of in-situ
RTVP-1 gene therapy will lower the incidence of local tumor recurrences when given to
patients prior to surgery. The second part of our hypothesis is that RTVP-1 gene therapy
will induce a systemic anti-tumor immune response, which will eliminate pre-existing
micrometastases in some of these patients and lower the overall failure rate.
While this Phase I study is not designed to answer these questions, we hope to obtain
mechanistic evidence in support of this hypothesis. A Phase II study will then be proposed
(and properly powered), to study the efficacy of this approach.
Based on our experience with HSV-tk and GCV in-situ gene therapy, it appears that maximal
immune stimulation occurs about 2 weeks following vector injection. Furthermore, repeat
injections of an adenoviral vector do not result in excess toxicity or in the generation of
anti-adenoviral antibodies sufficient to suppress vector activity. We propose here an
intraprostatic injection of RTVP-1 in an adenoviral vector 4-6 weeks prior to radical
prostatectomy, in order to allow full expression of the gene therapy tissue effects.
Inclusion Criteria:
- Histologic proof of prostatic adenocarcinoma without evidence of regional and/or
distant metastasis, clinical stage T1c, T2 or T3 with high grade disease (Gleason's 7
- 10) on initial biopsy, or PSA greater than 10 ng/ml with any stage or Gleason
score.
- Recent (equal to or less than 1 month prior to study entry) negative bone scan and CT
scan of abdomen/pelvis.
- Life expectancy of at least 10 years.
- Appropriate surgical candidate for radical prostatectomy and a performance status of
equal to or less than 2 (Zubrod scale).
- Patients should have adequate bone marrow function defined as an absolute peripheral
granulocyte count equal to or greater than 1,500 and platelet count of equal to or
greater than 100,000, adequate hepatic function with a bilirubin equal to or less
than 1.5 mg per cent and SGPT less than 2 x the upper limits of normal, adequate
renal function defined as serum creatinine equal to or less than 2.0 mg per cent.
- Patients must have normal coagulation profile (PT, PTT) and no history of substantial
non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only
(for control of central line patency).
- Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study, in keeping with the policies of the institution.
Exclusion Criteria:
- Previous or current hormonal treatment, chemotherapy, radiation therapy,
immunotherapy or other investigational status drug within the past 4 weeks.
- Unable to tolerate transrectal ultrasound.
- Patients who are not appropriate surgical candidates for radical prostatectomy based
on the evaluation of co-existent medical diseases and competing causes of death.
- Patients with uncontrolled cardiac, hepatic, renal or neurologic/psychiatric
disorders are not eligible.
- Patients who are HIV positive or have chronic hepatitis B or C infections are not
eligible (because of possible immune effects of these conditions).
- Patients with a history of primary or secondary immunodeficiency or patients taking
immunosuppressive drugs such as corticosteroids continuously for greater than 4
months [greater than 5 mg hydrocortisone/day] are ineligible. (The experimental
treatment being evaluated in this protocol depends on an intact immune system.
Patients who have a decreased immune competence may be less responsive to the
experimental treatment and more susceptible to its toxicities.)
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Assessment of safety/toxicity
Outcome Time Frame:
After treatment with 3-6 patients per cohort level, the patients will be assessed for the frequency of complications to be assured that they do not exceed those anticipated.
Safety Issue:
Yes
Principal Investigator
Dov Kadmon, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Baylor College of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
H-11112
NCT ID:
NCT00403221
Start Date:
August 2006
Completion Date:
April 2011
Related Keywords:
- Prostatic Neoplasms
- Gene therapy
- Prostate cancer
- Immunology, Angiogenesis inhibition
- Phase I clinical trial
- Neoplasms
- Prostatic Neoplasms
Name | Location |
|---|---|
| Baylor College of Medicine - Scott Department of Urology | Houston, Texas 77030 |
