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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.
 
ClinicalTrials.gov Identifier: NCT00403221
Recruitment Status : Completed
First Posted : November 23, 2006
Last Update Posted : February 10, 2012
Sponsor:
Information provided by (Responsible Party):
Dov Kadmon, Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE November 21, 2006
First Posted Date  ICMJE November 23, 2006
Last Update Posted Date February 10, 2012
Study Start Date  ICMJE August 2006
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2008)
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. ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 22, 2006)
Assessment of safety/toxicity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2008)
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. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2006)
  • To collect data on the morphologic and cytotoxic changes in the radical prostatectomy specimen
  • To assess local and systemic immunostimulatory activity
  • To assess the tumor neovascularity/antiangiogenic effects
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I - Pre-Radical Prostatectomy RTVP-1 Gene Therapy for Prostate Cancer
Official Title  ICMJE 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)
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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE 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.

Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 9, 2012)
19
Original Enrollment  ICMJE
 (submitted: November 22, 2006)
36
Actual Study Completion Date  ICMJE April 2011
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00403221
Other Study ID Numbers  ICMJE H-11112
P50CA058204 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dov Kadmon, Baylor College of Medicine
Study Sponsor  ICMJE Baylor College of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dov Kadmon, M.D. Baylor College of Medicine
PRS Account Baylor College of Medicine
Verification Date February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP