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

The Methodist Hospital Research Institute (TMHRI)

Status and phase: Unknown; Phase 2

Conditions: High-risk Prostate Cancer; Prostate Cancer

Treatments: Procedure: Radical prostatectomy; Drug: Valacyclovir; Drug: Leuprolide Acetate; Radiation: Brachytherapy, External beam radiotherapy; Drug: Bicalutamide; Drug: HSV-Tk

Study type: Interventional

Funder types: Other

Identifiers

NCT03541928

Pro00017515

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

60 participants in 1 patient group

Gene Therapy, ADT, RT, and Surgery

Experimental group

Description:

The 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.

Treatment:

Drug: HSV-Tk

Drug: Bicalutamide

Radiation: Brachytherapy, External beam radiotherapy

Drug: Leuprolide Acetate

Drug: Valacyclovir

Procedure: Radical prostatectomy