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

9 februari 2012 bijgewerkt door: Dov Kadmon, Baylor College of Medicine

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 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).

Studie Overzicht

Toestand

Voltooid

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

19

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • Baylor College of Medicine - Scott Department of Urology

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Mannelijk

Beschrijving

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.)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Assessment of safety/toxicity
Tijdsspanne: 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.
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.

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
To collect data on the morphologic and cytotoxic changes in the radical prostatectomy specimen
Tijdsspanne: Tumor response as measured by cytoreduction is not likely to be the major effect of the treatment.
Tumor response as measured by cytoreduction is not likely to be the major effect of the treatment.

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Onderzoekers

  • Hoofdonderzoeker: Dov Kadmon, M.D., Baylor College of Medicine

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 augustus 2006

Primaire voltooiing (Werkelijk)

1 april 2011

Studie voltooiing (Werkelijk)

1 april 2011

Studieregistratiedata

Eerst ingediend

21 november 2006

Eerst ingediend dat voldeed aan de QC-criteria

22 november 2006

Eerst geplaatst (Schatting)

23 november 2006

Updates van studierecords

Laatste update geplaatst (Schatting)

10 februari 2012

Laatste update ingediend die voldeed aan QC-criteria

9 februari 2012

Laatst geverifieerd

1 februari 2012

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • H-11112
  • P50CA058204 (Subsidie/contract van de Amerikaanse NIH)

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