Clinical trial NCT03541928: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: High-risk Prostate Cancer
Prostate Cancer
Keywords: gene therapy
untreated prostate cancer
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2018-05-31
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Biochemical control rate
timeFrame: 5-year biochemical disease free survival rate
Secondary outcomes:
measure: Overall survival rate
timeFrame: 5-year overall survival rate
measure: Pathologic complete response rate
timeFrame: After prostatectomy
measure: Safety based on questionnaire and clinical adverse event monitoring
timeFrame: 5-year post treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: E. Brian Butler, MD
role: PRINCIPAL_INVESTIGATOR
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