Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

Trial Title: Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

NCT ID: NCT05686798

Condition: Malignant Glioma of Brain
Astrocytoma
Malignant Astrocytoma
Brain Tumor
Glioma
Brain Cancer
Glioblastoma
Glioblastoma Multiforme
GBM

Conditions: Official terms:
Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Suicide

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Description: Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral
Arm group label: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS Arm

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.

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. 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. 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: - 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Henry Ford Health System

Address:
City: Detroit
Zip: 48202
Country: United States

Status: Recruiting

Contact:
Last name: Tobias Walbert, MD, PhD

Phone: 313-916-2723
Email: twalber1@hfhs.org

Start date: November 29, 2022

Completion date: October 2024

Lead sponsor:
Agency: Henry Ford Health System
Agency class: Other

Source: Henry Ford Health System

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05686798