Prostatic NeoplasmsPhase 1/2NCT01913106
HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer
A Phase 1/2 study testing HSV-tk +Valacyclovir in Combination with Brachytherapy in people with Prostatic Neoplasms, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to conduct a Phase I - II clinical trial to extend preclinical studies involving in situ HSV-tk + Valacyclovir gene therapy in combination with brachytherapy for recurrent prostate cancer. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- HSV-tk +Valacyclovir in Combination with Brachytherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brian Butler, MD contact
United States1 site, 1 recruiting
- Recruiting
Houston Methodist
Houston, Texas, 77030
Brent Bell, PA-C, 713-394-1105, bcbell@tmhs.org
Edward B Butler, MD, ebutler@tmhs.org
About this study
Official title: Phase I-II Study HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer With or Without Metastatic Disease
The purpose of this study is to conduct a Phase I - II clinical trial to extend preclinical studies involving in situ HSV-tk + Valacyclovir gene therapy in combination with brachytherapy for recurrent prostate cancer. This will provide a novel therapeutic approach to prostate cancer and hopefully impact on the development of metastatic disease and the control of preexisting metastasis.
Read the 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.
- Conditions
- Prostatic Neoplasms
- Being tested
- HSV-tk +Valacyclovir in Combination with Brachytherapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSV-tk +Valacyclovir in Combination with BrachytherapyDrug
Also called IND 13567
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.
| Study group | Role | What they receive |
|---|---|---|
| HSV-tk + Valacyclovir and Brachytherapy | Experimental | 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. Receives: Drug: HSV-tk +Valacyclovir in Combination with Brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
1. Safety based on standard laboratory and clinical adverse event monitoring
Measured: 5-year biochemical disease free survival rate
Secondary outcomes (2)
Local control survival (measured by PSA and biopsy)
Measured: 5-year biochemical disease free survival rate
Evaluate immunological markers
Measured: 5-year post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2013 (estimated)
- Study startJun 2007
- Primary completionDec 2018 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edward B Butler, MD, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01913106
- Sponsor's protocol ID
- Pro00000601
- Other IDs
- IRB 0107-0009
- Status last verified
- Jun 2016
- First submitted
- 25 Jul 2013
- Last updated
- 1 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer With or Without Metastatic Disease
- ClinicalTrials.gov ID
- NCT01913106
- Acronym / sponsor ID
- Pro00000601
- Conditions
- Prostatic Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 31 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to conduct a Phase I - II clinical trial to extend preclinical studies involving in situ HSV-tk + Valacyclovir gene therapy in combination with brachytherapy for recurrent prostate cancer. This will provide a novel therapeutic approach to prostate cancer and hopefully impact on the development of metastatic disease and the control of preexisting metastasis.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSV-tk + Valacyclovir and Brachytherapy | Experimental | Drug: HSV-tk +Valacyclovir in Combination with BrachytherapyYou 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. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HSV-tk +Valacyclovir in Combination with BrachytherapyAlso: IND 13567The 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. | Drug | HSV-tk + Valacyclovir and Brachytherapy |
Primary outcome
1. Safety based on standard laboratory and clinical adverse event monitoring
Time frame: 5-year biochemical disease free survival rate
2 secondary outcomes
Local control survival (measured by PSA and biopsy)
Time frame: 5-year biochemical disease free survival rate
Evaluate immunological markers
Time frame: 5-year post treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Butler, MD contact
Edward B Butler, MD principal investigator
The Methodist Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HSV-tk +Valacyclovir in Combination with Brachytherapy in people with Prostatic Neoplasms, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brent Bell, PA-C (713-394-1105, bcbell@houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1. Safety based on standard laboratory and clinical adverse event monitoring (time frame: 5-year biochemical disease free survival rate). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2016; AzTrials last refreshed its copy on 30 Oct 2026.