Clinical Trials /

Phase II High Risk Prostate Cancer Trial Using Gene & Androgen Deprivation Therapies, Radiotherapy, & Surgery

NCT03541928

Description:

This is a prospective phase II study to assess the efficacy and toxicity of HSV-tk+ valacyclovir gene therapy in combination with androgen deprivation therapy, brachytherapy, external beam radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II High Risk Prostate Cancer Trial Using Gene & Androgen Deprivation Therapies, Radiotherapy, & Surgery
  • Official Title: Phase II Study Evaluating HSV-tk + Valacyclovir Gene Therapy in Combination With Androgen Deprivation Therapy, Brachytherapy, External Beam Radiotherapy, and Prostatectomy for High-Risk Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: Pro00017515
  • NCT ID: NCT03541928

Conditions

  • High-risk Prostate Cancer
  • Prostate Cancer

Interventions

DrugSynonymsArms
HSV-TkGene therapy, AdV-tk gene therapy, Herpes simplex virus thymidine kinaseGene Therapy, ADT, RT, and Surgery
ValacyclovirValtrexGene Therapy, ADT, RT, and Surgery
BicalutamideCasodexGene Therapy, ADT, RT, and Surgery
Leuprolide AcetateLupronGene Therapy, ADT, RT, and Surgery

Purpose

This is a prospective phase II study to assess the efficacy and toxicity of HSV-tk+ valacyclovir gene therapy in combination with androgen deprivation therapy, brachytherapy, external beam radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer.

Detailed Description

      This phase II study plans to assess efficacy and toxicity of HSV-tk+ valacyclovir gene
      therapy in combination with androgen deprivation therapy, brachytherapy, external beam
      radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer patients.

      Clinical response as evaluated by changes in serum PSA level and digital rectal examination
      as well as by histological alterations on re-biopsy and prostatectomy such as the presence of
      apoptosis, necrosis, tumor proliferation and immunologic response, will be assessed following
      HSV-tk + valacyclovir treatment. Blood samples will be taken for systemic immunological
      response, blood counts and liver functions tests. Toxicity will be graded by the Common
      Terminology Criteria for Adverse Events (CTCAE) and Radiation Therapy Oncology Group (RTOG)
      neuro-toxicity scores (See Appendices). Additionally, patients will be followed closely to
      assess nadir PSA, freedom from PSA-progression, and freedom from local and distant
      progression and overall survival.
    

Trial Arms

NameTypeDescriptionInterventions
Gene Therapy, ADT, RT, and SurgeryExperimentalThe investigational gene therapy, ADV/HSV-tk, will be administered by injection into the prostate at 5 x 10[11] virus particles (1.25 x 10[11] virus particles per tumor quadrant in 4 quadrants) on day 0 and day 30. The recommended dose of Valacyclovir for this trial is 2 g orally t.i.d. for 14 days (day 1 to day 15 and days 31 to 45). The recommended dose for Bicalutamide therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening). Leuprolide acetate 7.5mg depot injection will be injected monthly for a total of 2 months.
  • HSV-Tk
  • Valacyclovir
  • Bicalutamide
  • Leuprolide Acetate

Eligibility Criteria

        Inclusion Criteria:

          -  All patients must have biopsy proven adenocarcinoma of the prostate

          -  Patients in should have at least one or more of the following characteristics PSA>20,
             Gleason score 8-10, Primary Gleason pattern 5, >4 cores with Gleason 8-10, and
             Clinical stage T3a-T4.

          -  No prior surgical, hormonal, or radiotherapy prostate treatment.

          -  ECOG performance status 0-1

          -  No evidence of metastatic disease or other malignancy (except squamous or basal cell
             skin cancers.

          -  Patients must have PSA within 3 months of entry.

          -  Signed informed consent to participate in the study must be obtained from patients
             after they have been fully informed of the nature and potential risks of the study by
             the investigator (or his/her designee) with the aid of written information.

          -  Willing to provide biopsies as required by the study.

          -  Patients must have adequate baseline organ function as assessed by the following
             laboratory values before initiating the protocol:

          -  serum creatinine < 1.5 mg%

          -  T. bilirubin < 2.5 mg%, ALT and AST < 2x normal

          -  Pts > 100,000/mm3 , ANC> 1500 mm , Hgb> 10gm%

          -  Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT)

        Exclusion Criteria:

          -  Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector
             therapy in the past 3 months.

          -  Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug within 3
             weeks of study treatment start.

          -  Evidence of metastatic disease

          -  Prostate volume >50cc

          -  Prior prostate surgery (hyperthermia, cryotherapy, etc.)

          -  Prior pelvic radiotherapy

          -  Prior androgen ablation hormonal therapy (except finasteride if discontinued > 3 mo.
             prior to enrollment)

          -  Patients on corticosteroids or any immunosuppressive drugs.

          -  History of liver disease, such as cirrhosis or active/chronic hepatitis B or C.

          -  History of or current alcohol misuse/abuse within the past 12 months.

          -  Known or suspected allergy or hypersensitivity to any component of the proposed
             regimen (gene vector/Valacyclovir).

          -  Inability to swallow food or any condition of the upper gastrointestinal tract that
             precludes administration of oral medications (Valacyclovir).

          -  No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or
             treated cancer from which the patient has been continuously disease free for more than
             5 years.

          -  Presence of active or suspected acute or chronic uncontrolled infection or history of
             immunocompromise, including a positive HIV test result.

          -  Patients < 18 years of age

          -  Unwilling or unable to comply with the study protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Biochemical control rate
Time Frame:5-year biochemical disease free survival rate
Safety Issue:
Description:measured by PSA

Secondary Outcome Measures

Measure:Overall survival rate
Time Frame:5-year overall survival rate
Safety Issue:
Description:Measured at the end of the study
Measure:Pathologic complete response rate
Time Frame:After prostatectomy
Safety Issue:
Description:Measured by pathologic result of prostatectomy
Measure:Safety based on questionnaire and clinical adverse event monitoring
Time Frame:5-year post treatment
Safety Issue:
Description:Measured by the Sexual Health Inventory for Men (SHIM), the International Prostate Symptoms Score (IPSS), and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Methodist Hospital System

Trial Keywords

  • gene therapy
  • untreated prostate cancer

Last Updated

October 24, 2018