Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.
NCT ID: NCT05686798
Last Updated: 2025-12-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
18 participants
INTERVENTIONAL
2022-11-29
2027-12-31
Brief Summary
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Detailed Description
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Patients with recurrent glioblastoma (GBM) or progressive high grade astrocytoma who are scheduled to undergo repeat surgery are eligible. After the removal of as much tumor tissue as possible, a modified oncolytic adenovirus is injected into the wall of the resection cavity and any residual tumor tissue. The goal of this study is to determine the maximum tolerated dose (MTD) of the injected adenovirus. This treatment is combined with a combination of oral 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy. Following the surgery, patients will be treated with fractionated radiosurgery (fSRS). Patients will be monitored for 30 days before they start on next line anti-cancer therapy.
Conditions
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Study Design
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NA
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS Arm
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.
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral
Interventions
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Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral
Eligibility Criteria
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Inclusion Criteria
To be eligible for this trial, the subjects must have:
* Histologically documented glioblastomas or anaplastic astrocytoma prior to the debulking surgery that is suspicious to have progressed on imaging. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiation while at least 4 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.
* Patients must be ≥ 18 years of age, able to provide informed consent and express a willingness to meet all the expected requirements of the protocol for the duration of the study.
* Must have recovered from toxicity (grade 2 or less) of prior therapy.
* Eligible for partial or total resection of the recurrent tumor
* No anticipated physical connection between post-resection tumor cavity and cerebral ventricle
* Karnofsky performance status (KPS) ≥ 60 at time of surgery
* No prior treatment of the tumor with gene or virus therapy, immunotherapy, brachytherapy, or implants of polymers containing chemotherapeutic agents (e.g. Gliadel Wafer)
* No immunosuppressive or immune disorder
* Baseline organ function testing intact
* Patients who are candidates for surgical debulking (re-resection) following recurrence of diseases based on multidisciplinary evaluation by neurosurgeons, radiation oncologists, neuro-radiologists, and neuro-oncologists.
2. Subjects must have adequate baseline organ function, as assessed by the following laboratory values, within 30 days before initiating the study therapy:
* Adequate renal function with creatinine clearance ≥ 50 mL/min/m2
* Platelet count ≥ 100,000/μL
* Absolute neutrophil count ≥ 1,000/μL
* Hemoglobin \> 10.0 g/dL
* Bilirubin \< 1.5 mg/dL; SGOT and SGPT \< 2.5 times upper limit of normal (ULN).
3. Women of child-bearing potential will be required to practice birth control for the duration of the treatment and for at least 90 days after surgery with intratumor virus inoculation. Men must use barrier protection for the duration of treatment and for at least 90 days after surgery with intratumor virus inoculation treatment.
Exclusion Criteria
* Serum antibodies to human immunodeficiency virus (HIV)
* Previous history of liver disease including autoimmune or viral hepatitis
* Positive serologic test for Hepatitis B or C at baseline
* Immunosuppressive therapy except for corticosteroid use
* Serious medical or psychiatric illness or concomitant medication, which, in the judgment of the investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trial
* Impaired immunity or susceptibility to serious viral infections
* Pregnant or lactating females
* Allergy to any product used on the protocol
* Patient is not able to undergo a brain MRI.
* Patients who are not eligible for debulking surgery or resection of recurrent disease will be considered ineligible.
18 Years
ALL
No
Sponsors
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Henry Ford Health System
OTHER
Responsible Party
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Tobias Walbert, MD, PhD
Principal Investigator
Principal Investigators
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Tobias Walbert, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Henry Ford Health System
Locations
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Henry Ford Health System
Detroit, Michigan, United States
Countries
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Central Contacts
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Facility Contacts
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References
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Ene CI, Fueyo J, Lang FF. Delta-24 adenoviral therapy for glioblastoma: evolution from the bench to bedside and future considerations. Neurosurg Focus. 2021 Feb;50(2):E6. doi: 10.3171/2020.11.FOCUS20853.
Mitchell LA, Lopez Espinoza F, Mendoza D, Kato Y, Inagaki A, Hiraoka K, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. Toca 511 gene transfer and treatment with the prodrug, 5-fluorocytosine, promotes durable antitumor immunity in a mouse glioma model. Neuro Oncol. 2017 Jul 1;19(7):930-939. doi: 10.1093/neuonc/nox037.
Kiyokawa J, Wakimoto H. Preclinical And Clinical Development Of Oncolytic Adenovirus For The Treatment Of Malignant Glioma. Oncolytic Virother. 2019 Oct 24;8:27-37. doi: 10.2147/OV.S196403. eCollection 2019.
Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF. Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther. 1993 Feb;4(1):39-69. doi: 10.1089/hum.1993.4.1-39.
Chen SH, Shine HD, Goodman JC, Grossman RG, Woo SL. Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3054-7. doi: 10.1073/pnas.91.8.3054.
Freytag SO, Rogulski KR, Paielli DL, Gilbert JD, Kim JH. A novel three-pronged approach to kill cancer cells selectively: concomitant viral, double suicide gene, and radiotherapy. Hum Gene Ther. 1998 Jun 10;9(9):1323-33. doi: 10.1089/hum.1998.9.9-1323.
Other Identifiers
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HFHS-21-02
Identifier Type: -
Identifier Source: org_study_id