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Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

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ClinicalTrials.gov Identifier: NCT05686798
Recruitment Status : Recruiting
First Posted : January 17, 2023
Last Update Posted : November 8, 2023
Sponsor:
Information provided by (Responsible Party):
Henry Ford Health System

Study Description
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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.

Condition or disease Intervention/treatment Phase
Malignant Glioma of Brain Astrocytoma Malignant Astrocytoma Brain Tumor Glioma Brain Cancer Glioblastoma Glioblastoma Multiforme GBM Biological: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS) Phase 1

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 29, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Ad5-yCD/mutTKSR39rep-ADP adenovirus and fSRS Arm
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)
Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral


Outcome Measures
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Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: 30 days ]
    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.


Secondary Outcome Measures :
  1. 1. Assessment of antitumor immune response [ Time Frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days. ]
    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).

  2. 2. Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts [ Time Frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days. ]
    Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts measured by flow cytometry

  3. Assessment of antitumor immune response by using antibodies against surface markers [ Time Frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days. ]
    Assessment of antitumor immune response by using antibodies against surface markers (CD3, CD56, CD4, CD8, CD45, CD69).


Other Outcome Measures:
  1. Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 [ Time Frame: Pre-surgery (day 0), 30 days, 90 days ]
    Assessment of quality of life (QOL) by using the European Organization for Research and Treatment of Cancer (EORTC) tools consisting of the EORTC QLQ-C30

  2. Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20 [ Time Frame: Pre-surgery (day 0), 30 days, 90 days ]
    Assessment of quality of life (QOL) by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05686798


Contacts
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Contact: Tobias Walbert, MD, PhD 3139162723 twalber1@hfhs.org
Contact: Nyati Shyam, PhD 734-272-1751 snyati1@hfhs.org

Locations
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United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Tobias Walbert, MD, PhD    313-916-2723    twalber1@hfhs.org   
Sponsors and Collaborators
Henry Ford Health System
Investigators
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Principal Investigator: Tobias Walbert, MD, PhD Henry Ford Health System
More Information
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Publications:

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Responsible Party: Henry Ford Health System
ClinicalTrials.gov Identifier: NCT05686798    
Other Study ID Numbers: HFHS-21-02
First Posted: January 17, 2023    Key Record Dates
Last Update Posted: November 8, 2023
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Glioma
Brain Neoplasms
Astrocytoma
Suicide
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
Self-Injurious Behavior
Behavioral Symptoms