Study of Stereotactic Radiosurgery to the Subventricular Zone in Malignant Gliomas

March 13, 2023 updated by: Northwell Health

Phase I Study of Subventricular Zone Tumor Stem Cell Stereotactic Radiosurgery With Standard of Care Chemoradiation Therapy in Newly Diagnosed Malignant Gliomas (WHO III and WHO IV Astrocytomas)

Several investigations suggest neural stem cells located in the subventricular region play an active role in promoting or even initiating cortical malignant glioma growth. Although normal appearing on neuroimaging, surgical specimens taken from this region show it contains malignant glioma stem-like cells. Some retrospective analyses found patients who received radiation therapy to this region during standard of care treatments lived longer than patients who did not.

The investigator's study hypothesizes (1) stereotactic radiosurgery of cancer stem-like cells in these regions will be well tolerated during standard of care therapy, (2) focused stereotactic radiosurgery will be more effective in destroying cancer stem cells than conventional radiation therapy, and (3) treatment will improve malignant glioma survival.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Since 2005, standard treatment for malignant gliomas includes surgery as extensive as possible to reduce tumor bulk without causing deficits, followed by temozolomide chemotherapy with radiation therapy to the surgical area plus an additional 1-2 cm margin around this cavity. Despite advances in surgical techniques and radiation delivery, 80% of tumors recur at the margins of the surgery, within the regions that were treated with radiation.

In 2014, different institutions found patients lived longer if part of the brain that looked normal received radiation therapy. This region was called the "subventricular zone" and was known to contain embryonic stem cells that formed the brain. Researchers believed this region contained cancer stem cells promoting tumor survival and growth. Some studies suggested this area might even represent another reservoir of malignant tumor cells.

During participation in this clinical trial, targeted radiation to the subventricular zone is given in addition to standard of care radiation and chemotherapy. The subventricular zone is divided into four regions and one of four regions on the same side as the tumor is treated, not the whole subventricular zone. Only patients scheduled to receive six weeks of standard therapy are eligible for participation. The additional radiation therapy is delivered over the course of one day. The study is not randomized and all patients will receive the experimental treatment. Patients complete regular evaluations over the next two years to monitor toxicity, which is the main concern of this Phase I study.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health Brain Tumor Center

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Consent to participate in a clinical trial
  • Confirmed WHO III or WHO IV malignant glioma, based upon Northwell Health neuropathology review. Outside cases must be submitted for central neuropathology review.
  • Completion of major surgical debulking procedure, defined as residual tumor volume of less than 20% original mass
  • Age greater than 18 years old. Children are not included because their disease behaves in a biologically distinct manner and there are already national clinical trials specific to them
  • Patients will not be excluded on the basis of advanced age (i.e., >75 years old), but there will need to be an intent to deliver standard chemoradiation therapy. Patients scheduled for accelerated radiation therapy are ineligible
  • Karnofsky performance status of 50 or higher. Patients may require considerable assistance and frequent medical care.
  • Willingness to sign HIPAA authorization that allows the investigators to continue to obtain clinical information even if patient leaves the study institution for care elsewhere in order to collect long term outcome and toxicity data.
  • Lobar tumor location (Frontal, temportal, parietal, occipital, or thalamic)

Exclusion Criteria:

  • Inability to consent to participate in a clinical trial, as determined during the standard of care practice evaluation of a malignant brain tumor patient.
  • Prior malignant glioma treatment less than 12 months prior to chemoradiation therapy, other than surgery with or without Gliadel wafer placement. Patients who received radiation therapy in the treatment of a lower grade malignancy (i.e., low grade glioma now transformed to WHO Grade III or WHO grade IV) are eligible as long as they are eligible for standard chemoradiation therapy and the radiation therapy delivered in the past was more than 12 months prior to planned chemoradiation therapy.
  • Any localized interstitial radiotherapy treatment
  • Concurrent clinical trial participation during standard of care therapy. Clinical trial participation is permitted in the event of recurrent disease.
  • Nonlobar tumor location (e.g., callosal, brainstem, or cerebellar tumors)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the principal investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the proposed regimen
  • Pregnancy is an exclusion criterion. Pregnant patients will not receive the study treatment. Women of childbearing age are routinely screened prior to radiation therapy administration for pregnancy. If found to be pregnant, then patient will not be offered participation in the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation (18Gy)
Receive additional dose of 18Gy to the subventricular zone
Radiation: Stereotactic Radiosurgery
Stereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care
Other Names:
  • Gamma Knife
Experimental: Dose Escalation (20Gy)
Receive additional dose of 20Gy to the subventricular zone
Radiation: Stereotactic Radiosurgery
Stereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care
Other Names:
  • Gamma Knife
Experimental: Dose Escalation (22Gy)
Receive additional dose of 22Gy to the subventricular zone
Radiation: Stereotactic Radiosurgery
Stereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care
Other Names:
  • Gamma Knife

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity of Therapy
Time Frame: 24 months
INCIDENCE OF TREATMENT-EMERGENT ADVERSE EVENTS AS DEFINED BY CTCAE criteria as well as BY steroid requirement
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 24 months
PFS measured by time to recurrence as well as pattern of recurrence
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Investigators

  • Principal Investigator: Alexis M Demopoulos, MD, Northwell Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

December 24, 2018

Primary Completion (Actual)

September 1, 2022

Study Completion (Actual)

September 1, 2022

Study Registration Dates

First Submitted

May 14, 2019

First Submitted That Met QC Criteria

May 20, 2019

First Posted (Actual)

May 21, 2019

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-0794

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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