Phase II High Risk Prostate Cancer Trial Using Gene & Androgen Deprivation Therapies, Radiotherapy, & Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03541928|
Recruitment Status : Recruiting
First Posted : May 31, 2018
Last Update Posted : October 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|High-risk Prostate Cancer Prostate Cancer||Drug: HSV-Tk Drug: Valacyclovir Drug: Bicalutamide Drug: Leuprolide Acetate Radiation: Brachytherapy, External beam radiotherapy Procedure: Radical prostatectomy||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||August 2, 2018|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||July 2023|
Experimental: Gene Therapy, ADT, RT, and Surgery
The investigational gene therapy, ADV/HSV-tk, will be administered by injection into the prostate at 5 x 10 virus particles (1.25 x 10 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.
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.
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.
Other Name: Valtrex
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.
Other Name: Casodex
Drug: Leuprolide Acetate
Leuprolide acetate 7.5 mg depot injection will be injected monthly for a total of 2 months.
Other Name: Lupron
Radiation: Brachytherapy, External beam radiotherapy
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.
Procedure: Radical prostatectomy
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.
Other Name: Prostatectomy
- Biochemical control rate [ Time Frame: 5-year biochemical disease free survival rate ]measured by PSA
- Overall survival rate [ Time Frame: 5-year overall survival rate ]Measured at the end of the study
- Pathologic complete response rate [ Time Frame: After prostatectomy ]Measured by pathologic result of prostatectomy
- Safety based on questionnaire and clinical adverse event monitoring [ Time Frame: 5-year post treatment ]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)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03541928
|Contact: Emily Hsiao, Ph.D.||firstname.lastname@example.org|
|Contact: Christine O'Reillyemail@example.com|
|United States, Texas|
|Houston Methodist Hospital||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Edward B Butler|
|Principal Investigator:||E. Brian Butler, MD||The Methodist Hospital System|