62 Participants Needed

Gene Therapy + Chemoradiotherapy for Glioblastoma

HM
DS
Overseen ByDavid S. Baskin, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: The Methodist Hospital Research Institute
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combining gene therapy, an antiviral drug, radiation, and standard cancer drugs for patients with aggressive brain tumors. The gene therapy helps make cancer cells more sensitive to the antiviral drug, while radiation and chemotherapy work to kill or stop the growth of these cells. The gene therapy has been studied for its ability to enhance the effectiveness of treatments for brain tumors.

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 have had any chemotherapy, radiotherapy, or immunotherapy within 3 weeks of starting the study. Also, you cannot be on immunosuppressive drugs, except for steroids for brain swelling.

Is the gene therapy treatment using ADV/HSV-tk generally safe for humans?

In studies involving humans, some patients experienced an increase in anti-adenovirus antibodies and short-term fever, while others had more frequent seizures. No other significant adverse events related to the gene therapy were reported.12345

What makes the Gene Therapy + Chemoradiotherapy treatment for glioblastoma unique?

This treatment combines gene therapy with chemoradiotherapy, using a virus to deliver a gene that makes cancer cells more sensitive to a drug, leading to tumor regression and long-term survival even in the presence of immune responses against the virus, which is a novel approach compared to standard treatments.56789

What data supports the effectiveness of the treatment ADV/HSV-tk for glioblastoma?

Research shows that using adenovirus vectors to deliver the herpes simplex virus thymidine kinase gene can lead to tumor regression and longer survival in brain cancer models, even when the immune system is active against the virus. This suggests that the treatment could be effective for glioblastoma.345710

Who Is on the Research Team?

DS

David S Baskin, MD

Principal Investigator

Houston Methodist Neurological Institute

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed glioblastoma or anaplastic astrocytoma, confirmed by biopsy. Participants must have a life expectancy of at least 12 weeks, be able to provide biopsies, and not have multifocal disease or brainstem involvement. They should not be on immunosuppressive drugs (except steroids), have liver disease, alcohol misuse/abuse in the past year, known allergies to treatment components, trouble swallowing pills, other active malignancies (with exceptions), untreated infections or severe drug abuse.

Inclusion Criteria

I am using effective birth control methods.
I can have a second HSV-tk treatment after 6 months.
My biopsy shows I have a specific brain tumor without it spreading in my brain.
See 10 more

Exclusion Criteria

I am under 18 years old.
I have not recently had chemotherapy, radiation, immunotherapy, or experimental drugs.
Active IV drug abuse or severe opioid abuse
See 14 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

HSV-tk gene therapy is injected during surgery, followed by valacyclovir for 14 days

2 weeks
1 visit (in-person)

Radiotherapy and Chemotherapy

Radiotherapy administered over 30 sessions (6 weeks) with concurrent chemotherapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment with MRI or CT every 6-8 weeks for the first year, then every 12-14 weeks

Up to 60 months

Optional Second Treatment

Participants can receive a second treatment of HSV-tk after 6 months

Not specified

What Are the Treatments Tested in This Trial?

Interventions

  • ADV/HSV-tk
Trial Overview The study tests the safety and effectiveness of gene therapy using ADV/HSV-tk combined with valacyclovir medication, radiotherapy (XRT), and chemotherapy in patients who are newly diagnosed with glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA).
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Experimental: ADV/HSV-tk (gene therapy)Experimental Treatment1 Intervention
Experimental: ADV/HSV-tk (gene therapy) The gene therapy investigational product, HSV-tk will be injected during the surgery. Within 24 hours valacyclovir will be given for 14 days. Radiotherapy will be administered over 30 sessions (over 6 weeks) starting within 9 days of surgery. Standard of care/routine chemotherapy will be started concurrent with the radiotherapy dependent on patient status based on best clinical judgment following the Stupp protocol. Patient can receive second treatment of HSV-tk after 6 months.

Find a Clinic Near You

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials
299
Recruited
82,500+

Published Research Related to This Trial

High-capacity adenovirus vectors (HC-Ads) carrying the herpes simplex virus type 1-thymidine kinase (TK) gene can induce tumor regression and improve long-term survival in a glioblastoma multiforme model, even when the immune system has pre-existing responses against the adenovirus.
In contrast, first-generation adenovirus vectors (Ad-TK) were ineffective in promoting tumor regression, highlighting the potential of HC-Ads as a more effective gene therapy strategy for treating this aggressive brain cancer.
High-capacity adenovirus vector-mediated anti-glioma gene therapy in the presence of systemic antiadenovirus immunity.King, GD., Muhammad, AK., Xiong, W., et al.[2021]
Adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene (tk) showed significant antitumor effects in an oral cancer model in mice, indicating its potential efficacy for treating solid tumors.
The treatment was found to be safe, as no cytopathic effects were observed in distant organs, and there were no significant changes in liver, renal, or bone marrow function after administration, even at high doses of the adenoviral vector.
Safety of in vivo adenovirus-mediated thymidine kinase treatment of oral cancer.Sewell, DA., Li, D., Duan, L., et al.[2019]
Adenovirus-mediated transfer of the HSV-tk gene significantly prolonged survival in rats with brain tumors when followed by ganciclovir (GCV) treatment, demonstrating its efficacy as a therapeutic approach.
Both adenovirus and retrovirus-mediated gene transfer of HSV-tk resulted in similar survival benefits, indicating that either method can be effective for treating brain tumors in this model, while other methods without GCV did not lead to tumor cell death.
Herpes simplex virus thymidine kinase gene therapy for rat malignant brain tumors.Vincent, AJ., Vogels, R., Someren, GV., et al.[2013]

Citations

High-capacity adenovirus vector-mediated anti-glioma gene therapy in the presence of systemic antiadenovirus immunity. [2021]
Safety of in vivo adenovirus-mediated thymidine kinase treatment of oral cancer. [2019]
Herpes simplex virus thymidine kinase gene therapy for rat malignant brain tumors. [2013]
Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. [2021]
[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on various cancer cells]. [2015]
Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. [2023]
Adenovirus-mediated gene therapy of experimental gliomas. [2013]
Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. [2023]
The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects. [2019]
Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. [2019]
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