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Malignant Glioma of BrainPhase 1NCT05686798

Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

A Phase 1 study testing Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS) in people with Malignant Glioma of Brain and Astrocytoma, run by Henry Ford Health System at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
29 Nov 2022to Dec 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with radiologic evidence of intracranial recurrence or progression of a previously diagnosed high-grade astrocytoma.
  • 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
Show all 19Show fewer
  • 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.
  • 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).
  • 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.

Who cannot join

  • Acute infection. Acute infection is defined by any viral, bacterial, or fungal infection that has required active treatment and caused oral temperature >38.5oC and/or clinically significant leukocytosis
  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Tobias Walbert, MD, PhD contact

3139162723

twalber1@hfhs.org

Nyati Shyam, PhD contact

734-272-1751

snyati1@hfhs.org

United States1 site, 1 recruiting

  • Henry Ford Health System

    Detroit, Michigan, 48202

    Tobias Walbert, MD, PhD, 3139162723, twalber1@hfhs.org

    Recruiting

Other trials in United States

About this study

Official title: Phase I Study of Replication-Competent Adenovirus-Mediated Double Suicide Gene Therapy With Stereotactic Radiosurgery in Patients With Recurrent or Progressive High Grade Astrocytomas

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.

Read the detailed description

Detailed study description:

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.

Being tested
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Medical subject headings
Astrocytoma, Brain Neoplasms, Glioma, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)Biological

    Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral

Study groups in NCT05686798
Study groupRoleWhat they receive
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS ArmExperimentalSubjects 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.
Receives: Biological: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose

    The primary objective is to determine the maximum tolerated dose of injected of Ad5-yCD/mutTKSR39rep-ADP adenovirus into the resection cavity at the time of surgery.

    Measured: 30 days

Secondary outcomes (3)

  1. 1. Assessment of antitumor immune response

    Assessment of antitumor immune response by serum levels of interferon-gamma (IFN-γ) measured by ELISA and will be described by pico-gram per milliliter (pg/mL).

    Measured: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.

  2. 2. Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts

    Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts measured by flow cytometry

    Measured: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.

  3. Assessment of antitumor immune response by using antibodies against surface markers

    Assessment of antitumor immune response by using antibodies against surface markers (CD3, CD56, CD4, CD8, CD45, CD69).

    Measured: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2023
  2. Study start29 Nov 2022
  3. Primary completionJan 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05686798
Sponsor's protocol ID
HFHS-21-02
Status last verified
Dec 2025
First submitted
16 Nov 2022
Last updated
16 Dec 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33524949

  • 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.

    PubMed 28387849

  • 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.

    PubMed 31750274

  • 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.

    PubMed 8384892

  • 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.

    PubMed 8159705

  • 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.

    PubMed 9650617

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS) in people with Malignant Glioma of Brain and Astrocytoma, run by Henry Ford Health System at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Tobias Walbert, MD, PhD (3139162723, twalber1@hfhs.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (time frame: 30 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05686798, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.

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