Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

Launched by HENRY FORD HEALTH SYSTEM · Jan 9, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with a type of brain cancer called high-grade astrocytoma, which often comes back after initial treatment. The researchers are combining a special type of virus therapy, known as oncolytic adenovirus mediated double suicide-gene therapy, with targeted radiation therapy to see how well it works and to find out the highest dose that patients can tolerate safely. This trial is currently looking for participants aged 18 and older who have evidence of tumor recurrence and are eligible for surgery to remove some of the tumor.

To participate, patients must have had a previous diagnosis of glioblastoma or anaplastic astrocytoma, must be able to give their informed consent, and must meet certain health criteria, such as having good kidney function and being free of severe side effects from prior treatments. Throughout the study, participants will receive the new therapy and will be closely monitored for their response and any side effects. It's important for candidates to be aware that the trial has specific eligibility requirements and that those who have had certain previous treatments or health issues may not qualify.

Gender

ALL

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.