Phase I Study of Replication-Competent Adenovirus-Mediated Double Suicide Gene Therapy With Stereotactic Radiosurgery in Patients With Recurrent or Progressive High Grade Astrocytomas

Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Phase 1
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

⁃ 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).

• 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.

Locations
United States
Michigan
Henry Ford Health System
RECRUITING
Detroit
Contact Information
Primary
Tobias Walbert, MD, PhD
twalber1@hfhs.org
3139162723
Backup
Nyati Shyam, PhD
snyati1@hfhs.org
734-272-1751
Time Frame
Start Date: 2022-11-29
Estimated Completion Date: 2026-10
Participants
Target number of participants: 18
Treatments
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.
Sponsors
Leads: Henry Ford Health System

This content was sourced from clinicaltrials.gov

Similar Clinical Trials