- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01913106
HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer
Phase I-II Study HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer With or Without Metastatic Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This investigational new drug application describes a proposed phase I/II study designed to assess the safety and efficacy of AdV-tk gene therapy in combination with standard brachytherapy for patients with locally recurrent prostate cancer after having failed radiation as a primary treatment with or without minimal metastasis. These patients do not have any standard treatment that has been demonstrated to have a high degree of efficacy in eradicating the tumor with a reasonable degree of safety. Thus, the potential risks associated with the use of gene therapy in this group would appear reasonable. This application is for use of a replication defective adenovirus vector (ADV/RSV-tk) delivering the HSV-tk gene as a biologic vector for gene therapy.
Direct introduction of therapeutic genes into malignant cells in vivo may provide an effective treatment of solid tumors such as prostate cancer. The herpes simplex virus thymidine kinase (HSV-tk) gene codes for an enzyme which phosphorylates the nucleoside analog ganciclovir (GCV) into an intermediate that is incorporated into newly synthesized DNA and terminates further replication, leading to cell death. Since normal mammalian cells do not possess this enzyme, cytotoxicity depends on the successful introduction and expression of the HSV-tk gene, phosphorylation of ganciclovir and synthesis of DNA. Non-dividing cells may express HSV-tk and phosphorylate ganciclovir but are not harmed since they do not synthesize DNA. This approach is especially suitable for the treatment of tumors where rapidly dividing tumor cells are adjacent to tissues made up largely of non-proliferating cells. Using human and animal models for prostate cancer we have demonstrated that adenovirus-mediated transfer of the HSV-tk gene resulted in sensitivity to ganciclovir in vitro and growth suppression of mouse prostate cancer in vivo.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Brent Bell, PA-C
- Phone Number: 713-394-1105
- Email: bcbell@houstonmethodist.org
Study Contact Backup
- Name: Brian Butler, MD
- Email: ebutler@houstonmethodist.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Houston Methodist
-
Contact:
- Brent Bell, PA-C
- Phone Number: 713-394-1105
- Email: bcbell@tmhs.org
-
Contact:
- Edward B Butler, MD
- Email: ebutler@tmhs.org
-
Principal Investigator:
- Edward B Butler, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- biopsy-proven local recurrence of prostate cancer without metastatic disease after the hormone therapy at least 2 year after the completion of definitive radiation therapy
- Zubrod performance status 0-1
- WBC ≥ 4,000/μl, platelets ≥ 100,000/μl
- hemoglobin ≥ 8.5 mg/dl
- normal partial thromboplastin time and prothrombin time
- bilirubin < 1.5 mg/dl, and AST and alanine aminotransferase < 2.5 times the upper limit of normal
- Serum creatinine ≤ 1.6 mg/dl
- Must undergo pre-treatment evaluation of tumor extent and tumor measurement
- Nutritional and general physical condition must be considered compatible with the proposed radio-therapeutic treatment
- Not on any other experimental therapeutic cancer treatment
- No active untreated infection
- No major medical or psychiatric illness
- International Prostate Symptom Score (IPSS) less than 15
- Signed study-specific consent form prior to study entry
- Prostate volume less than 50 cc
- PSA > 10ng/ml within the past 3 months may enter study
EXCLUSION CRITERIA:
- Symptomatic metastasis disease
- Patients with a life expectancy < 10 years
- Patients on corticosteroids or any immunosuppressive drugs.
- HIV + patients
- Patients with acute infections (viral, bacterial, or fungal infections requiring therapy)
- Patients with cirrhosis.
- Patients with collagen vascular diseases
- International Prostate Symptom Score (IPSS) greater than 15
- Prostate volume greater than 50 cc
- Second active cancer except cutaneous cancer
- Patients with history of allergies to valacyclovir, acyclovier or who cannot take oral pills
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HSV-tk + Valacyclovir and Brachytherapy
You will be given an antibiotic (Ciproflaxin) to take twice a day beginning the day before the procedure, and continuing for a total of 3 - 5 days.
You will also be given 4 pills called (Valtrex) valacyclovir to take three times a day for 14 days, beginning the day before the procedure.
You will be given a pill diary in which you will record each dose of valacyclovir that you take.
You will receive brachytherapy (radioactive seed placement) the day after you begin taking your pills.
After the radioactive seeds are placed, while you are still in the operating room, you will receive an injection into your prostate of 1 or 2 ml (one-fifth or two-fifths of a teaspoon) of a solution of the vector carrying the gene.
|
The investigators insert a gene from a herpes simplex virus (HSV), which is a small piece of the basic structure of the virus, into the prostate gland tumor cells.
The gene is called the thymidine kinase (tk) gene, which the cell uses to make a protein that can change valacyclovir, The way the tk gene will be transported into the tumor cells is by using a vector or "vehicle" to carry the tk gene into the cells.
In this case the vector is a virus - an adenovirus.
Scientists at the Department of Cell and Gene Therapy at The Methodist Hospital removed a portion of the adenovirus' genetic material that allows it to replicate so that it cannot cause infections.
In place of the removed genetic material the scientists inserted the tk gene.
Now the vector can carry the tk gene into tumor cells.
When the vector/gene combination gets into tumor cells, it inserts itself into the cells' command center (nucleus) and tells the tumor cells to begin making thymidine kinase protein.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
1. Safety based on standard laboratory and clinical adverse event monitoring
Time Frame: 5-year biochemical disease free survival rate
|
5-year biochemical disease free survival rate
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Local control survival (measured by PSA and biopsy)
Time Frame: 5-year biochemical disease free survival rate
|
5-year biochemical disease free survival rate
|
Evaluate immunological markers
Time Frame: 5-year post treatment
|
5-year post treatment
|
Collaborators and Investigators
Investigators
- Principal Investigator: Edward B Butler, MD, The Methodist Hospital Research Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00000601
- IRB 0107-0009 (Other Identifier: Houston Methodist Research Institute IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostatic Neoplasms
-
Australian and New Zealand Urogenital and Prostate...Peter MacCallum Cancer Centre, AustraliaRecruitingCastration Resistant Prostatic CancerAustralia
-
MacroGenicsRecruitingCastration-Resistant Prostatic Cancer | Androgen-Independent Prostatic Cancer | Androgen-Insensitive Prostatic Cancer | Androgen-Resistant Prostatic Cancer | Hormone Refractory Prostatic CancerSpain, Australia, Korea, Republic of, United States, France, Italy, Belgium, United Kingdom, Poland
-
British Columbia Cancer AgencySanofi; Ozmosis Research Inc.UnknownMetastatic Castration-Resistant Prostatic CancerCanada, Australia
-
Janssen Research & Development, LLCCompletedCastration-Resistant Prostatic NeoplasmsCanada, Belgium, United States, Spain, Netherlands, Italy, Russian Federation
-
Technische Universität DresdenRecruitingOligometastatic Disease | Prostatic Cancer, Castration-ResistantGermany
-
Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
-
Yinghao SunNot yet recruitingCastration-Resistant Prostatic Cancer
-
Institut Claudius RegaudWithdrawnProstatic Cancer, Castration-ResistantFrance
-
University Hospital, GrenobleTerminatedCastration-resistant Prostate CancerFrance
-
Michael Graham PhD, MDUniversity of Iowa; Holden Comprehensive Cancer CenterActive, not recruitingProstate Cancer | Prostatic Neoplasms, Castration-Resistant | Prostatic Neoplasm | Prostatic Cancer Recurrent | Prostatic Cancer MetastaticUnited States
Clinical Trials on HSV-tk +Valacyclovir in Combination with Brachytherapy
-
The Methodist Hospital Research InstituteMerck Sharp & Dohme LLCCompletedMetastatic Non-small Cell Lung Cancer | Metastatic Triple-negative Breast CancerUnited States
-
Eric Bernicker, MDTerminatedNonsquamous Nonsmall Cell Neoplasm of Lung | Metastatic Uveal Melanoma | Lung Squamous Cell Carcinoma Stage IVUnited States
-
David BüchserRecruiting
-
The Methodist Hospital Research InstituteRecruitingProstate Cancer | High-risk Prostate CancerUnited States
-
Centre Georges Francois LeclercRecruitingTo Evaluate the Rate of Digestive and Urinary ToxicityFrance
-
Shen LinUnknownColorectal Cancer | Esophageal Squamous Cell Carcinoma | Biliary Tract Cancer | Targeted Therapy | HER2China
-
AkesoNot yet recruiting
-
Sun Yat-sen UniversityRecruitingPeripheral T-cell LymphomaChina
-
Peking Union Medical CollegeNot yet recruiting
-
Aurora Health CareRecruiting