62 Participants Needed

Gene Therapy + Chemoradiotherapy for Glioblastoma

DS
HM
Overseen ByHelga M Jones
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?

Study to assess the safety and efficacy of HSV-tk (gene therapy), valacyclovir, radiotherapy and chemotherapy in recurrent glioblastoma multiforme.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must not have had any cytotoxic chemotherapy, radiotherapy, immunotherapy, or investigational drugs for your brain tumor within 3 weeks of starting the study treatment.

Is the gene therapy treatment involving 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. It is unique because it combines cytotoxic (cell-killing) and immune-stimulatory effects, which are not typically present in standard glioblastoma treatments.26789

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.245910

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 recurrent anaplastic astrocytoma or glioblastoma multiforme, confirmed by biopsy. Participants must have a life expectancy of at least 12 weeks, be recovered from previous treatments, and not have multifocal disease or brainstem involvement. They should use effective birth control and agree to provide biopsies. Those with other active cancers (except certain skin cancers), pregnant or breastfeeding women, and individuals unable to take oral medications are excluded.

Inclusion Criteria

I have a confirmed diagnosis of recurrent anaplastic astrocytoma or glioblastoma without multiple tumor locations or brainstem involvement.
I may have cancer cells in the fluid around my brain and spinal cord.
I have signed and understand the consent form for this study.
See 11 more

Exclusion Criteria

I haven't had chemotherapy, radiation, immunotherapy, or experimental drugs for my brain tumor in the last 3 weeks.
I have no active cancer except for certain skin cancers or treated cancers that have been clear for over 5 years.
Active IV drug abuse or severe opioid abuse
See 15 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 and radiotherapy over 10 sessions within 2 weeks

2 weeks
10 visits (in-person for radiotherapy)

Chemotherapy

Standard of care chemotherapy is administered concurrent with or after radiotherapy

Varies based on patient status

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

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

What Are the Treatments Tested in This Trial?

Interventions

  • ADV/HSV-tk
Trial Overview The study tests the combination of HSV-tk gene therapy with valacyclovir medication, stereotactic body radiotherapy (SBRT), and chemotherapy in patients who have had their glioblastoma return. It aims to evaluate the safety and effectiveness of this approach.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: ADV/HSV-tk (gene therapy)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

David Baskin MD

Lead Sponsor

Trials
1
Recruited
60+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials
114
Recruited
2,900+

The Methodist Hospital Research Institute

Collaborator

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]
[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on various cancer cells]. [2015]
Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. [2021]
Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. [2023]
Adenovirus-mediated gene therapy of experimental gliomas. [2013]
The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects. [2019]
Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. [2023]
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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