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

NCT00403221 | Completed Phase 1

• 2 other identifiers: H-11112P50CA058204
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostatic Neoplasms

Keywords

Gene therapy; Prostate cancer; Immunology, Angiogenesis inhibition; Phase I clinical trial

Outcome Measures

Primary Outcomes (1)

• Assessment of safety/toxicity

  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 Outcomes (1)

• To collect data on the morphologic and cytotoxic changes in the radical prostatectomy specimen

  Tumor response as measured by cytoreduction is not likely to be the major effect of the treatment.

Interventions

RTVP-1 Gene GENETIC

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine - Scott Department of Urology

Houston, Texas, 77030, United States

Location

Related Publications (5)

• Satoh T, Timme TL, Saika T, Ebara S, Yang G, Wang J, Ren C, Kusaka N, Mouraviev V, Thompson TC. Adenoviral vector-mediated mRTVP-1 gene therapy for prostate cancer. Hum Gene Ther. 2003 Jan 20;14(2):91-101. doi: 10.1089/104303403321070793.

  PMID: 12614561 BACKGROUND

• Ren C, Li L, Goltsov AA, Timme TL, Tahir SA, Wang J, Garza L, Chinault AC, Thompson TC. mRTVP-1, a novel p53 target gene with proapoptotic activities. Mol Cell Biol. 2002 May;22(10):3345-57. doi: 10.1128/MCB.22.10.3345-3357.2002.

  PMID: 11971968 BACKGROUND

• Ren C, Li L, Yang G, Timme TL, Goltsov A, Ren C, Ji X, Addai J, Luo H, Ittmann MM, Thompson TC. RTVP-1, a tumor suppressor inactivated by methylation in prostate cancer. Cancer Res. 2004 Feb 1;64(3):969-76. doi: 10.1158/0008-5472.can-03-2592.

  PMID: 14871827 BACKGROUND

• Naruishi K, Timme TL, Kusaka N, Fujita T, Yang G, Goltsov A, Satoh T, Ji X, Tian W, Abdelfattah E, Men T, Watanabe M, Tabata K, Thompson TC. Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer. Cancer Gene Ther. 2006 Jul;13(7):658-63. doi: 10.1038/sj.cgt.7700919. Epub 2006 Feb 17.

  PMID: 16485011 BACKGROUND

• Ren C, Ren CH, Li L, Goltsov AA, Thompson TC. Identification and characterization of RTVP1/GLIPR1-like genes, a novel p53 target gene cluster. Genomics. 2006 Aug;88(2):163-72. doi: 10.1016/j.ygeno.2006.03.021. Epub 2006 May 22.

  PMID: 16714093 BACKGROUND

Related Links

• Scott Department of Urology Clinical Trials

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Dov Kadmon, M.D.

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Urology

Study Record Dates

• First Submitted: November 21, 2006
• First Posted: November 23, 2006
• Study Start: August 1, 2006
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: February 10, 2012

Record last verified: 2012-02

Locations

US (1)