Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

NCT05686798 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HFHS-21-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Glioma of Brain; Malignant Astrocytoma; Brain Tumor; Glioma; Brain Cancer; Glioblastoma; Glioblastoma Multiforme; GBM; Astrocytoma

Outcome Measures

Primary Outcomes (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.

  30 days

Secondary Outcomes (3)

• 1. Assessment of antitumor immune response

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

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

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

• Assessment of antitumor immune response by using antibodies against surface markers

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

Other Outcomes (2)

• Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30

  Pre-surgery (day 0), 30 days, 90 days

• Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20

  Pre-surgery (day 0), 30 days, 90 days

Study Arms (1)

Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS Arm

EXPERIMENTAL

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.

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

Interventions

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

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

Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Henry Ford Health System: lead

Study Sites (1)

Henry Ford Health System

Detroit, Michigan, 48202, United States

RECRUITING

Related Publications (6)

• 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.

  PMID: 33524949 BACKGROUND

• 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.

  PMID: 28387849 BACKGROUND

• 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.

  PMID: 31750274 BACKGROUND

• 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.

  PMID: 8384892 BACKGROUND

• 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.

  PMID: 8159705 BACKGROUND

• 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.

  PMID: 9650617 BACKGROUND

MeSH Terms

Conditions

Astrocytoma; Brain Neoplasms; Glioma; Glioblastoma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Tobias Walbert, MD, PhD

  Henry Ford Health System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Walbert, MD, PhD

CONTACT

3139162723; twalber1@hfhs.org

Nyati Shyam, PhD

CONTACT

734-272-1751; snyati1@hfhs.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2022
• First Posted: January 17, 2023
• Study Start: November 29, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)