18 Participants Needed

Gene Therapy + Radiotherapy for Brain Tumor

TW
NS
Overseen ByNyati Shyam, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Henry Ford Health System
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The primary goal of this Phase I study is to determine the maximum tolerated dose of oncolytic adenovirus mediated double suicide-gene therapy in combination with fractionated stereotactic radiosurgery in patients with recurrent high-grade astrocytoma undergoing resection.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have recovered from previous treatments and cannot be on immunosuppressive therapy, except for corticosteroids.

What data supports the effectiveness of the treatment Gene Therapy + Radiotherapy for Brain Tumor?

Research shows that combining gene therapy with radiation can significantly enhance the destruction of tumor cells. In studies, this approach led to marked tumor regression and improved cure rates in various cancer models, suggesting it could be effective for brain tumors as well.12345

Is the gene therapy combined with radiotherapy safe for humans?

Research shows that the gene therapy using adenovirus (Ad5-CD/TKrep and Ad5-yCD/mutTKSR39rep-ADP) combined with radiotherapy has been tested in humans, particularly for prostate cancer, and has been found to be generally safe. Most side effects were mild or moderate, and no severe toxicities were reported, indicating that this treatment approach is safe for human use.13467

What makes the Gene Therapy + Radiotherapy treatment for brain tumors unique?

This treatment is unique because it combines a gene therapy using a modified adenovirus to deliver a fusion gene that makes tumor cells more sensitive to antiviral drugs and radiation, enhancing the effectiveness of radiotherapy. This approach, known as double suicide gene therapy, uses two enzyme/prodrug systems to increase tumor cell death and improve treatment outcomes compared to traditional therapies.12389

Research Team

Tobias Walbert, MD | Henry Ford Health ...

Tobias Walbert, MD, PhD, MPH

Principal Investigator

Henry Ford Health System

Eligibility Criteria

Adults with recurrent high-grade astrocytoma eligible for tumor resection, not previously treated with certain gene/immunotherapies or implants. Must have good organ function, no immune disorders, and agree to birth control. Excludes those with serious illnesses that could interfere with the trial, pregnant/lactating women, allergy to protocol products, impaired immunity, inability to undergo MRI, acute infections or liver disease.

Inclusion Criteria

I can care for myself but may need occasional help.
Hemoglobin > 10.0 g/dL
It has been over 4 weeks since my last non-nitrosourea chemotherapy.
See 18 more

Exclusion Criteria

Pregnant or lactating females
My immune system is weak and I easily get serious viral infections.
I am not on immunosuppressive therapy, except for corticosteroids.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Adenovirus Injection

Patients undergo repeat surgery for tumor resection followed by intratumoral injection of modified oncolytic adenovirus

1 day
1 visit (in-person)

Treatment

Participants receive fractionated stereotactic radiosurgery combined with oral 5-fluorocytosine and valganciclovir prodrug therapy

30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days
Multiple visits (in-person and virtual) at days 3, 7, 14, 21, 30, and 90

Treatment Details

Interventions

  • Ad5-yCD/mutTKSR39rep-ADP adenovirus
  • Fractionated Stereotactic Radiosurgery (fSRS)
Trial OverviewThe study tests a maximum tolerated dose of Ad5-yCD/mutTKSR39rep-ADP adenovirus combined with fractionated stereotactic radiosurgery in patients undergoing surgery for recurrent high-grade astrocytoma. It's a Phase I trial focused on safety and dosage levels.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS ArmExperimental Treatment1 Intervention
Subjects will receive a single intratumoral injection of the Ad5-yCD/mutTKSR39rep-ADP adenovirus at one of three dose levels beginning at 1 x 1011 vp and escalating in half-log (3-fold) increments to 1 x 1012 vp, along with the same dose of fractionated stereotactic radiosurgery until unacceptable toxicity, disease progression, or withdrawal of consent.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Henry Ford Health System

Lead Sponsor

Trials
334
Recruited
2,197,000+

Findings from Research

The replication-competent adenovirus Ad5-CD/TKrep showed significant antitumor activity against cervical carcinoma in vivo, especially when combined with double prodrug therapy (5-FC + GCV) and radiation therapy.
This trimodal treatment approach led to remarkable tumor regression and a 100% cure rate, highlighting its potential for future clinical trials in cancer therapy.
Double suicide gene therapy augments the antitumor activity of a replication-competent lytic adenovirus through enhanced cytotoxicity and radiosensitization.Rogulski, KR., Wing, MS., Paielli, DL., et al.[2020]
In a study involving 72 nude mice with human glioblastoma, combining adenoviral HSV TK gene therapy with radiation therapy significantly prolonged median survival by 5 days without increasing toxic side effects.
The combination treatment also reduced neurological symptoms and delayed the onset of deficits, suggesting a safer and more effective approach for glioblastoma therapy.
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]
The combination of adenoviral-directed cytosine deaminase (CD) gene therapy with radiation therapy significantly enhanced tumor regression in human cancer xenografts, with larger tumors showing a reduction to 11% of their original volume after treatment.
Smaller tumors treated with the same combined approach not only showed significant regression but also continued to shrink over time, with 43% of these tumors cured by day 26, indicating that this gene therapy could improve local tumor control and potentially increase survival rates.
Virally directed cytosine deaminase/5-fluorocytosine gene therapy enhances radiation response in human cancer xenografts.Hanna, NN., Mauceri, HJ., Wayne, JD., et al.[2013]

References

Double suicide gene therapy augments the antitumor activity of a replication-competent lytic adenovirus through enhanced cytotoxicity and radiosensitization. [2020]
The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects. [2019]
Virally directed cytosine deaminase/5-fluorocytosine gene therapy enhances radiation response in human cancer xenografts. [2013]
A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. [2020]
Radiosensitization and anti-tumour effects of cytosine deaminase and thymidine kinase fusion suicide gene in human adenoid cystic carcinoma cells. [2017]
Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. [2021]
Second-generation replication-competent oncolytic adenovirus armed with improved suicide genes and ADP gene demonstrates greater efficacy without increased toxicity. [2021]
Selective enhancement by an antiviral agent of the radiation-induced cell killing of human glioma cells transduced with HSV-tk gene. [2014]
Radiosensitization of human glioma cells in vitro and in vivo with acyclovir and mutant HSV-TK75 expressed from adenovirus. [2019]