Gene Therapy + Chemoradiotherapy for Glioblastoma

Recruiting in Palo Alto (17 mi)

Overseen by David S Baskin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: David Baskin MD

Must not be taking: Immunosuppressants, Immunotherapy

Disqualifiers: Liver disease, Alcohol abuse, HIV, others

No Placebo Group

Trial Summary

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.

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. ^{1 2 3 4 5}

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. ^{1 2 4 6 7}

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. ^{1 5 8 9 10}

Research Team

David S Baskin, MD

Principal Investigator

Houston Methodist Neurological Institute

Eligibility Criteria

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.

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

Trial Timeline

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

Treatment Details

Interventions

• ADV/HSV-tk (Virus Therapy)

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.

Participant Groups

Group I: ADV/HSV-tk (gene therapy) Experimental Treatment 1 Intervention

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 10 sessions (over 2 weeks) starting within 9 days of surgery. Standard of care/routine chemotherapy will be started concurrent or after completion of the radiotherapy dependent on patient status based on best clinical judgment. Patient can receive second treatment of HSV-tk after 6 months

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Houston Methodist Neurological Institute Houston, TX

Who Is Running the Clinical Trial?

David Baskin MD

Lead Sponsor

Trials

1

Patients Recruited

60+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Patients Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Patients Recruited

82,500+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of in vivo adenovirus-mediated thymidine kinase treatment of oral cancer. Sewell, DA., Li, D., Duan, L., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Herpes simplex virus thymidine kinase gene therapy for rat malignant brain tumors. Vincent, AJ., Vogels, R., Someren, GV., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on various cancer cells]. Zhou, JF., Chen, G., Lu, YP., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. Candolfi, M., Yagiz, K., Foulad, D., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Sandmair, AM., Loimas, S., Puranen, P., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated gene therapy of experimental gliomas. Perez-Cruet, MJ., Trask, TW., Chen, SH., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects. Nestler, U., Wakimoto, H., Siller-Lopez, F., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. Umemura, Y., Orringer, D., Junck, L., et al.[2023]

The study developed a retroviral vector that combines two therapeutic genes, HSV-TK and IL-2, which showed higher expression in differentiated thyroid carcinoma cells and led to significant tumor reduction in both in vitro and in vivo models.

Using ganciclovir with the IL-2/HSV-TK combination resulted in complete eradication of anaplastic tumors and over 80% reduction in differentiated thyroid carcinomas, demonstrating that this combined gene therapy approach is more effective than using IL-2 alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. Barzon, L., Bonaguro, R., Castagliuolo, I., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

High-capacity adenovirus vector-mediated anti-glioma gene therapy in the presence of systemic antiadenovirus immunity. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety of in vivo adenovirus-mediated thymidine kinase treatment of oral cancer. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Herpes simplex virus thymidine kinase gene therapy for rat malignant brain tumors. [2013]

4. China pubmed.ncbi.nlm.nih.gov

[Killing effect of adenovirus vector-mediated herpes simplex virus thymidine kinase gene recombinant construct on various cancer cells]. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Release of HMGB1 in response to proapoptotic glioma killing strategies: efficacy and neurotoxicity. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated gene therapy of experimental gliomas. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Gene therapy of thyroid cancer via retrovirally-driven combined expression of human interleukin-2 and herpes simplex virus thymidine kinase. [2019]