Gene Therapy + Brachytherapy for Prostate Cancer

Overseen By Brent Bell, PA-C

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Symptomatic metastasis, HIV, Cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for prostate cancer that has returned after radiation therapy. It explores gene therapy (using HSV-tk + Valacyclovir) alongside brachytherapy (a type of internal radiation therapy). The goal is to determine if this approach can better control cancer and prevent its spread. Men who have had a biopsy confirming their prostate cancer has returned, without spreading elsewhere, and who completed hormone therapy at least two years ago might be suitable candidates. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on corticosteroids or any immunosuppressive drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the HSV-tk + Valacyclovir treatment is generally safe for people in clinical trials. This treatment can reduce PSA levels, indicators of prostate cancer, in some patients without major safety concerns.

Brachytherapy, a procedure involving the placement of small radioactive seeds in the prostate, has also proven safe. Studies indicate that patients undergoing this treatment often experience good results with minimal risks, including effective cancer control over several years.

This trial combines both treatments to determine if they work even better together. Each treatment has demonstrated a strong safety record individually. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of gene therapy with brachytherapy for prostate cancer because it introduces a novel mechanism of action. Unlike traditional treatments, which typically involve surgery, radiation, or hormone therapy, this approach uses a modified herpes simplex virus (HSV-tk) combined with the antiviral drug valacyclovir to target and kill cancer cells directly. This gene therapy is delivered directly into the prostate, offering a targeted attack on cancer cells while minimizing harm to surrounding healthy tissue. The integration of brachytherapy further enhances the treatment by providing localized radiation, potentially increasing the effectiveness and precision of cancer cell eradication. This innovative combination holds promise for more effective and less invasive treatment outcomes.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants will receive a combination of HSV-tk gene therapy with Valacyclovir and brachytherapy. Research has shown that this combination may be promising for treating prostate cancer. Specifically, studies have found that using HSV-tk with Valacyclovir can significantly shrink tumors, with some treatments reducing them by up to 61%. This therapy increases effectiveness by making cancer cells more sensitive to the treatment. Brachytherapy, which involves placing small radioactive seeds in or near the tumor, is already a well-known treatment for prostate cancer and has improved survival rates for many patients. Together, these treatments might better control cancer and potentially reduce its spread. ^{1 2 5 6 7}

Who Is on the Research Team?

Edward B Butler, MD

Principal Investigator

The Methodist Hospital Research Institute

Are You a Good Fit for This Trial?

Men with biopsy-proven recurrent prostate cancer, no metastasis, and who've had hormone therapy and radiation. They must have a PSA >10ng/ml, good organ function, no major illnesses or second active cancers, not be on immunosuppressants or other experimental treatments, and able to take oral pills.

Inclusion Criteria

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

Exclusion Criteria

HIV + patients

My prostate is larger than 50 cc.

I do not have any current infections needing treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HSV-tk + Valacyclovir therapy in combination with brachytherapy. Valacyclovir is taken for 14 days, starting the day before brachytherapy.

2 weeks

1 visit (in-person) for brachytherapy and gene therapy injection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brachytherapy
• HSV-tk + Valacyclovir

Trial Overview The trial is testing HSV-tk + Valacyclovir gene therapy combined with brachytherapy for men whose prostate cancer has returned. It's in early stages (Phase I - II) to see if it can prevent the spread of cancer or control existing metastasis.

How Is the Trial Designed?

Group I: HSV-tk + Valacyclovir and Brachytherapy Experimental Treatment 1 Intervention

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.

Brachytherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Approved in European Union as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer
• Brain tumors

Approved in Canada as Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Brachytherapy, which involves the permanent implantation of radioactive seeds, shows promising results for treating early-stage prostate cancer, particularly in patients with favorable tumor characteristics, achieving biochemical failure rates comparable to radical prostatectomy.

While acute urinary retention occurred in 1%-14% of patients, long-term side effects were low (less than 5%), and a high percentage (86%-96%) of patients maintained sexual potency after treatment, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic overview of the evidence for brachytherapy in clinically localized prostate cancer. Crook, J., Lukka, H., Klotz, L., et al.[2018]

Brachytherapy, particularly with iodine-125 seeds, has been used effectively as a treatment for localized prostatic adenocarcinoma, showing a 15-year local control rate of 51% based on a study of 1119 patients.

Lymph node involvement is a significant prognostic factor for treatment outcomes, and there is a need for prospective randomized trials to compare brachytherapy with other treatment options like radical prostatectomy and external irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brachytherapy in prostatic adenocarcinoma]. Haie-Meder, C., Court, B., Perrin, JL., et al.[2006]

Brachytherapy for localized prostate cancer shows comparable clinical effectiveness to radical prostatectomy and external beam radiation, based on a systematic review of five observational studies, although no randomized controlled trials were found.

There is a lack of data on overall or disease-free survival rates and long-term costs, indicating that while short-term costs are similar, more research is needed to assess long-term outcomes and cost-effectiveness of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness. Norderhaug, I., Dahl, O., Høisaeter, PA., et al.[2019]

In a study of 130 patients treated with permanent I-125 seed implants for prostate cancer, the procedure showed a high biochemical relapse-free survival rate of 98.9% at one year and 87.8% at two years, indicating its efficacy in managing organ-confined prostate cancer.

The treatment was associated with low rates of acute toxicity, with only 1.4% experiencing mild rectal toxicity and 4.3% requiring intervention for acute urinary retention, suggesting that the procedure is well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Retrospective study of 130 patients with organconfined prostate cancer treated with brachytherapy]. Aguiló Lucía, F., Suárez Novo, JF., Correa Generoso, R., et al.[2019]

Permanent seed brachytherapy is a suitable treatment option for patients with low-risk localized prostate cancer, characterized by specific criteria such as T1-2 stage, PSA levels under 10 ng/mL, and well-differentiated cancer (Gleason score less than 7).

The 10-year outcomes in terms of cancer control and side effects from brachytherapy are comparable to other standard treatments like radical prostatectomy and external beam radiation therapy, highlighting its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Techniques, indications and results of permanent prostate brachytherapy for localized prostate cancer]. Bladou, F., Thuret, R., Gravis, G., et al.[2019]

Brachytherapy, both low-dose-rate (LDR) and high-dose-rate (HDR), is safe and feasible for renal transplant recipients (RTRs) with localized prostate cancer, as shown in a study of 3 RTR patients with stable renal function.

None of the RTR patients experienced disease progression or significant adverse effects from radiation therapy during a median follow-up of 44 months, indicating that their oncological outcomes are comparable to those of non-transplanted patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose-Rate and High-Dose-Rate Brachytherapy for Localized Prostate Cancer in ABO-Incompatible Renal Transplant Recipients. Tasaki, M., Kasahara, T., Kaidu, M., et al.[2019]

High-dose-rate brachytherapy (HDR-BT) for prostate cancer can be effectively performed under local anesthesia, as demonstrated in a study involving 11 patients who underwent 22 implantations.

Patients reported a manageable pain level during the procedure, with scores ranging from 2 to 6, indicating that local anesthesia is a viable option that can improve resource efficiency and expand treatment availability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial high-dose-rate brachytherapy and local anesthesia for prostate cancer: a feasibility report. Pellizzon, AC.[2021]

Prostate brachytherapy, particularly with permanent implants, has shown comparable long-term effectiveness to surgery for selected patients with localized prostate cancer, with lower rates of incontinence and impotence.

While urinary toxicity can occur in the months following the procedure, advancements in imaging and dosimetry have improved the safety and precision of brachytherapy, making it a promising option for more patients as the incidence of prostate cancer rises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brachytherapy for prostate cancer: old concept, new techniques]. Cosset, JM., Flam, T., Thiounn, N., et al.[2011]

Iodine-125 prostate seed brachytherapy shows high rates of biochemical control for prostate cancer in renal transplant recipients, with all four patients in the study remaining free of PSA progression after an average follow-up of 44 months.

The treatment demonstrated minimal toxicity, as there were no peri-operative complications and all patients maintained normal kidney function, suggesting it is a safe alternative to traditional surgery and radiotherapy for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iodine-125 prostate seed brachytherapy in renal transplant recipients: an analysis of oncological outcomes and toxicity profile. Beydoun, N., Bucci, J., Malouf, D.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9098556/

The 45-month therapy outcomes of permanent seed ... In prostate cancer patients, permanent seed implantation using iodine-125 seeds resulted in similar biochemical recurrence-free survival to ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1687850725002572

Meta-analysis of treatment effects for localized prostate ... The effect of BT seed implantation in treating localized prostate cancer is better than that of EBRT. The 5-year overall survival rate of patients is higher.

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)89749-3/fulltext

The prognosis of patients with prostate cancer receiving ... We study a relationship between prostate volume (PV) and prognosis in 6721 prostate cancer patients treated by permanent seed implantation (PI)

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1472866/

Advances in Brachytherapy - PMC - PubMed Central - NIH Currently, it is estimated that 30% to 40% of all patients with prostate cancer receive seed implantation as part of their treatment. Significant advances in ...

5. emedicine.medscape.com emedicine.medscape.com/article/453349-overview

Brachytherapy (Radioactive Seed Implantation Therapy) in ... HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Pelvic irradiation was suggested ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2287888223000041

The oncologic and safety outcomes of low-dose-rate ... The 7-year biochemical progression-free survival of LDR brachytherapy was significantly higher than that of DE-EBRT both in intermediate- and high-risk patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11355220/

Outcomes of I-125 Low-Dose-Rate Brachytherapy in ... In conclusion, this study reinforces the efficacy and safety of LDR brachytherapy for localized prostate cancer. The favorable clinical outcomes ...