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

Primary Purpose

High-risk Prostate Cancer, Prostate Cancer

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

HSV-Tk

Valacyclovir

Bicalutamide

Leuprolide Acetate

Brachytherapy, External beam radiotherapy

Radical prostatectomy

About this trial

This is an interventional treatment trial for High-risk Prostate Cancer focused on measuring gene therapy, untreated prostate cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept 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.

Sites / Locations

Houston Methodist HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gene Therapy, ADT, RT, and Surgery

Arm 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.

Outcomes

Primary Outcome Measures

Biochemical control rate

measured by PSA

Secondary Outcome Measures

Overall survival rate

Measured at the end of the study

Pathologic complete response rate

Measured by pathologic result of prostatectomy

Safety based on questionnaire and clinical adverse event monitoring

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)

Full Information

NCT ID

NCT03541928

First Posted

May 10, 2018

Last Updated

April 5, 2021

Sponsor

The Methodist Hospital Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT03541928

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

August 2, 2018 (Actual)

Primary Completion Date

July 2023 (Anticipated)

Study Completion Date

July 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Methodist Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High-risk Prostate Cancer, Prostate Cancer

Keywords

gene therapy, untreated prostate cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gene Therapy, ADT, RT, and Surgery

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

HSV-Tk

Other Intervention Name(s)

Gene therapy, AdV-tk gene therapy, Herpes simplex virus thymidine kinase

Intervention Description

Injection of the HSV-tk gene therapy product in four quadrants of prostate to enhance the immune system via "bystander effect" in which cytotoxicity is conferred to non-transduced neighboring cells. In vivo bystander effects are likely due to a combination of host immunological responses and to gap junction-mediated transport of phosphorylated prodrug metabolites to surrounding cells.

Intervention Type

Drug

Intervention Name(s)

Valacyclovir

Other Intervention Name(s)

Valtrex

Intervention Description

The recommended dose for this trial is 2 g orally t.i.d. for 14 days (day 1 to day 15 and days 31 to 45). This dose has been calculated to give a similar AUC as 10 mg/kg of intravenous acyclovir administered every 8 hours. This is the same dose regimen used in a previous phase I clinical trial of ADV/HSV-tk plus acyclovir and topotecan in patients with recurrent ovarian cancer.

Intervention Type

Drug

Intervention Name(s)

Bicalutamide

Other Intervention Name(s)

Casodex

Intervention Description

The recommended dose for Bicalutamide therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that Bicalutamide be taken at the same time each day. The use of an oral antiandrogen with medical castration for the treatment of prostate cancer is referred to as combined androgen blockade (CAB). Compared with LHRH-agonist monotherapy, CAB with bicalutamide did not reduce overall QoL but provided an early improvement in QoL related to lower urinary tract symptoms and pain.

Intervention Type

Drug

Intervention Name(s)

Leuprolide Acetate

Other Intervention Name(s)

Lupron

Intervention Description

Leuprolide acetate 7.5 mg depot injection will be injected monthly for a total of 2 months.

Intervention Type

Radiation

Intervention Name(s)

Brachytherapy, External beam radiotherapy

Other Intervention Name(s)

HDR, EBRT

Intervention Description

On day 60, patient will undergo high dose rate (HDR) Brachytherapy. The patient will have 8-14 needle catheters inserted under ultrasound guidance. CT simulation and radiation treatment planning will be performed. The needle catheters will be connected to an HDR afterloader containing an Iridium 192 source. A single dose of 1250cGy will be delivered.

Intervention Type

Procedure

Intervention Name(s)

Radical prostatectomy

Other Intervention Name(s)

Prostatectomy

Intervention Description

approximately 2-3 weeks after radiotherapy completion, patient will undergo radical retropubic prostatectomy. Use of laparoscopy or robotic assistance will be at the urologist's discretion. Lymph node dissection will be performed.

Primary Outcome Measure Information:

Title

Biochemical control rate

Description

measured by PSA

Time Frame

5-year biochemical disease free survival rate

Secondary Outcome Measure Information:

Title

Overall survival rate

Description

Measured at the end of the study

Time Frame

5-year overall survival rate

Title

Pathologic complete response rate

Description

Measured by pathologic result of prostatectomy

Time Frame

After prostatectomy

Title

Safety based on questionnaire and clinical adverse event monitoring

Description

Time Frame

5-year post treatment

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emily Hsiao, Ph.D.

Phone

713-383-5115

khsiao@houstonmethodist.org

First Name & Middle Initial & Last Name or Official Title & Degree

Christine O'Reilly

Phone

713-394-1107

coreilly@houstonmethodist.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

E. Brian Butler, MD

Organizational Affiliation

The Methodist Hospital Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Houston Methodist Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Edward B Butler

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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