RECRUITING

Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

Conditions

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2022-11-29

Study Completion:2024-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05686798

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subjects with radiologic evidence of intracranial recurrence or progression of a previously diagnosed high-grade astrocytoma. * 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.	* 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.

Inclusion Criteria

Exclusion Criteria

1. Subjects with radiologic evidence of intracranial recurrence or progression of a previously diagnosed high-grade astrocytoma.
* 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.

* 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.

Contacts and Locations

Study Contact

Tobias Walbert, MD, PhD

CONTACT

3139162723

twalber1@hfhs.org

Nyati Shyam, PhD

CONTACT

734-272-1751

snyati1@hfhs.org

Principal Investigator

Tobias Walbert, MD, PhD

PRINCIPAL_INVESTIGATOR

Henry Ford Health System

Study Locations (Sites)

Henry Ford Health System

Detroit, Michigan, 48202

United States

Collaborators and Investigators

Sponsor: Henry Ford Health System

Tobias Walbert, MD, PhD, PRINCIPAL_INVESTIGATOR, Henry Ford Health System

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-29

Study Completion Date2024-10

Study Record Updates

Study Start Date2022-11-29

Study Completion Date2024-10

Terms related to this study

Additional Relevant MeSH Terms

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