What side effects are associated with this type of intervention?

Common treatments for Glioblastoma, such as gene therapy (e.g., HSV-tk), radiotherapy, and chemotherapy, have several known side effects. Gene therapy can lead to immune responses such as the development of anti-vector antibodies. Radiotherapy is associated with acute and subacute radiation encephalopathy, which can cause headaches, focal neurologic symptoms, and nausea. Chemotherapy agents like temozolomide can cause headaches, changes in semen parameters, and potential reproductive harm. Additionally, these treatments can lead to neurocognitive dysfunction, fatigue, and increased risk of infections.

What other types of research exist?

Promising novel alternatives to HSV-tk gene therapy for Glioblastoma patients include: 1) Checkpoint inhibitor immunotherapy (e.g., pembrolizumab, nivolumab) which enhances the immune system's ability to target tumor cells. 2) CAR T-cell therapy, which involves modifying a patient's T-cells to better recognize and attack cancer cells. 3) Tumor Treating Fields (TTF), a non-invasive treatment that uses electric fields to disrupt cancer cell division. 4) Oncolytic virus therapy, such as DNX-2401, which uses engineered viruses to selectively infect and kill tumor cells. 5) Personalized vaccine therapies, which are designed to elicit a targeted immune response against tumor-specific antigens.

← Back to Search

Virus Therapy

Gene Therapy + Chemoradiotherapy for Glioblastoma

Q: What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma, including temozolomide, which is a standard chemotherapy drug used in conjunction with radiotherapy. While specific gene therapies like HSV-tk (which involves inserting the HSV-tk gene into tumor cells to make them susceptible to antiviral drugs like valacyclovir) are still under investigation, other innovative approaches such as tumor-treating fields (Optune) have also been approved. These treatments aim to improve survival and quality of life for patients with Glioblastoma.

Phase 1 & 2

Recruiting

Led By David S. Baskin, MD

Research Sponsored by The Methodist Hospital Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

All patients must have frozen section biopsy proven anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal disease or brainstem involvement

No evidence of other active malignancy except squamous or basal cell skin cancers

Must not have

Patients under 18 years of age

Recent cytotoxic chemotherapy, RT, immunotherapy, or investigational drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 60 months measured in months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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).

What are the potential side effects?

Potential side effects may include reactions related to gene therapy such as flu-like symptoms, headache and nausea; complications from taking valacyclovir like kidney issues; effects from radiotherapy including skin irritation and fatigue; plus typical chemotherapy side effects such as hair loss, nausea/vomiting and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My biopsy shows I have a specific brain tumor without it spreading in my brain.

Select...

I have no active cancer except possibly skin cancer.

Select...

I have been newly diagnosed with a high-grade brain tumor.

Select...

I had surgery for a brain tumor and need another one for remaining cancer.

Select...

I am fully active or can carry out light work.

Select...

My organ functions are within normal ranges according to recent tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am under 18 years old.

Select...

I have not recently had chemotherapy, radiation, immunotherapy, or experimental drugs.

Select...

My cancer has spread to multiple areas or the brainstem.

Select...

I cannot swallow pills due to a condition in my upper digestive tract.

Select...

My cancer has spread to my brainstem or is widely affecting the lining of my brain and spinal cord.

Select...

I have an active skin infection or wound that hasn't been treated.

Select...

I do not have an ongoing infection or a weakened immune system.

Select...

I do not have an active brain infection.

Select...

I have liver disease, like cirrhosis or hepatitis B/C.

Select...

I have no active cancer except for certain allowed types.

Select...

I am currently taking drugs that suppress my immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 60 months measured in months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 60 months measured in months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 60 months measured in months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival in months up to 5 years from Study drug administration (Day 0)

Secondary study objectives

Progression free survival assessments will be done every 6-8 weeks for 1st year thereafter every 12-14 weeks until disease progression or death

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Glioblastoma include gene therapy, chemotherapy, and targeted molecular therapies. Gene therapy, such as HSV-tk, involves inserting a gene into tumor cells to make them susceptible to antiviral drugs like valacyclovir, leading to targeted cell destruction. Chemotherapy agents like temozolomide damage the DNA of cancer cells, inhibiting their ability to replicate. Targeted molecular therapies focus on specific pathways or mutations within the tumor cells, such as inhibiting growth factor receptors or other critical signaling pathways. Understanding these mechanisms is crucial for Glioblastoma patients as it helps in selecting the most effective treatment strategy tailored to the tumor's specific characteristics, potentially improving outcomes and minimizing side effects.

Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma.Recent advances in experimental molecular therapeutics for malignant gliomas.