Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations.
Chibawanye I Ene, Juan Fueyo, Frederick F Lang
https://pubmed.ncbi.nlm.nih.gov/33524949Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID05686798
Phase I Study of Adenovirus-Mediated Double Suicide Gene Therapy Combined With Stereotactic Radiosurgery in Recurrent or Progressive High-Grade Astrocytomas
Led by Henry Ford Health System · Updated on 2025-12-16
18
Participants Needed
1
Research Sites
47 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying patients with recurrent glioblastoma or progressive high-grade astrocytoma who are scheduled for repeat surgery. This Phase I trial aims to find the highest safe dose of a modified oncolytic adenovirus given with fractionated stereotactic radiosurgery in these patients. The study combines gene therapy with radiation to evaluate potential treatment options for these brain tumors. Participants will receive a single injection of the Ad5-yCD/mutTKSR39rep-ADP adenovirus directly into the tumor area after surgery, at one of three increasing dose levels. This gene therapy is combined with oral medications 5-fluorocytosine and valganciclovir, followed by fractionated stereotactic radiosurgery. Treatment continues until unacceptable side effects, tumor progression, or withdrawal. The study includes a monitoring period before starting any new cancer therapy. During the study, patients will be closely monitored for safety and immune response through blood tests and assessments at multiple time points before and after surgery, up to 90 days. Researchers will measure the maximum tolerated dose and observe changes in immune markers. The study lasts through treatment and follow-up, with a 30-day observation before other therapies begin, ensuring comprehensive safety and response evaluation.
CONDITIONS
Brief Title
Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Radiologic evidence of intracranial recurrence or progression of high-grade astrocytoma
- Histologically confirmed glioblastoma or anaplastic astrocytoma prior to surgery
- At least 3 months since last radiation, 4 weeks since non-nitrosourea chemotherapy, 6 weeks since nitrosourea chemotherapy
- Age 18 years or older and able to provide informed consent
- Recovered from prior therapy toxicity of grade 2 or less
- Eligible for partial or total resection of recurrent tumor
- No physical connection between tumor cavity and cerebral ventricle
- Karnofsky performance status of 60 or higher at surgery
- No prior gene or virus therapy, immunotherapy, brachytherapy, or chemotherapeutic polymer implants
- No immunosuppressive or immune disorders
- Adequate organ function as per lab tests within 30 days before therapy
- Women of childbearing potential must use birth control during treatment and 90 days after
- Men must use barrier protection during treatment and 90 days after
- Candidate for surgical debulking after disease recurrence based on expert evaluation
You will not qualify if you...
- Acute infection requiring treatment with fever over 38.5°C or significant leukocytosis
- Positive HIV antibodies
- History of liver disease including autoimmune or viral hepatitis
- Positive hepatitis B or C serology
- Use of immunosuppressive therapy except corticosteroids
- Serious medical or psychiatric illness that may interfere with treatment or trial completion
- Impaired immunity or vulnerability to serious viral infections
- Pregnant or breastfeeding women
- Allergy to any study products
- Unable to undergo brain MRI
- Not eligible for tumor debulking or resection of recurrent disease
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Surgery and Immediate Post-operative Care
Duration - Single day for surgery and injection
Participants undergo repeat surgery for tumor removal. After surgery, a modified adenovirus is injected into the tumor cavity and any residual tumor tissue.
1 visit (in-person surgery and injection)
Treatment
Duration - Duration varies until toxicity, progression, or withdrawal
Participants receive oral prodrug therapy combined with fractionated stereotactic radiosurgery (fSRS) until unacceptable toxicity, disease progression, or withdrawal from the trial.
Multiple visits for fractionated radiosurgery and monitoring
Follow-up
Duration - Up to 90 days post-treatment
Participants are monitored for safety and immune response after treatment for up to 90 days.
Visits at pre-surgery, days 3, 7, 14, 21, 30, and 90
Trial Site Locations
Total: 1 location
1
Henry Ford Health System
Detroit, Michigan, United States, 48202
Actively Recruiting
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Research Team
T
Tobias Walbert, MD, PhD
N
Nyati Shyam, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
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E H Oldfield, Z Ram, K W Culver...
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S H Chen, H D Shine, J C Goodman...
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https://pubmed.ncbi.nlm.nih.gov/9650617