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Phase I - Pre-Radical Prostatectomy RTVP-1 Gene Therapy for Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00403221
Recruitment Status : Completed
First Posted : November 23, 2006
Last Update Posted : February 10, 2012
Information provided by (Responsible Party):
Dov Kadmon, Baylor College of Medicine

Brief Summary:
The purpose of this study is to conduct a Phase I clinical trial involving in situ RTVP-1 gene therapy for prostate cancer. We will conduct necessary safety evaluations on a new adenovirus that contains the human genes for RTVP-1. This virus will then be evaluated for safety in men with prostate cancer prior to radical prostatectomy. Based on the preclinical data, we hope that this treatment will induce not only a local cytotoxic and antiangiogenic effect but also, a systemic antitumor immune response capable of eradicating micrometastatic disease (the reason for recurrence in many of these patients).

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Genetic: RTVP-1 Gene Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : August 2006
Actual Primary Completion Date : April 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine

Intervention Details:
  • Genetic: RTVP-1 Gene

    Cohort Level #1 1.0 x 1010vp Cohort Level #2 5.0x1010vp Cohort Level #3 1.0 x 1011vp Cohort Level #4 5.0x1011vp Cohort Level #5 1.0 x 1012vp Cohort Level #6 5.0x1012vp

    One dose only followed by a radical prostatectomy 4 weeks later.

Primary Outcome Measures :
  1. Assessment of safety/toxicity [ 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. ]

Secondary Outcome Measures :
  1. To collect data on the morphologic and cytotoxic changes in the radical prostatectomy specimen [ Time Frame: Tumor response as measured by cytoreduction is not likely to be the major effect of the treatment. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00403221

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United States, Texas
Baylor College of Medicine - Scott Department of Urology
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
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Principal Investigator: Dov Kadmon, M.D. Baylor College of Medicine
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Responsible Party: Dov Kadmon, Professor of Urology, Baylor College of Medicine Identifier: NCT00403221    
Other Study ID Numbers: H-11112
P50CA058204 ( U.S. NIH Grant/Contract )
First Posted: November 23, 2006    Key Record Dates
Last Update Posted: February 10, 2012
Last Verified: February 2012
Keywords provided by Dov Kadmon, Baylor College of Medicine:
Gene therapy
Prostate cancer
Immunology, Angiogenesis inhibition
Phase I clinical trial
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases