Study of Stereotactic Radiosurgery to the Subventricular Zone in Malignant Gliomas

NCT03956706 | Withdrawn FDA Device

• 1 other identifier: 18-0794
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma; Astrocytoma, Grade III; Astrocytoma, Grade IV; Malignant Glioma

Keywords

SRS; Stereotactic Radiosurgery; Glioblastoma; Astrocytoma; Grade III; Grade IV; Glioma; Malignant Glioma; Gamma Knife

Outcome Measures

Primary Outcomes (1)

• Toxicity of Therapy

  INCIDENCE OF TREATMENT-EMERGENT ADVERSE EVENTS AS DEFINED BY CTCAE criteria as well as BY steroid requirement

  24 months

Secondary Outcomes (1)

• Progression-free survival

  24 months

Study Arms (3)

Dose Escalation (18Gy)

EXPERIMENTAL

Receive additional dose of 18Gy to the subventricular zone

Radiation: Stereotactic Radiosurgery

Dose Escalation (20Gy)

EXPERIMENTAL

Receive additional dose of 20Gy to the subventricular zone

Radiation: Stereotactic Radiosurgery

Dose Escalation (22Gy)

EXPERIMENTAL

Receive additional dose of 22Gy to the subventricular zone

Radiation: Stereotactic Radiosurgery

Interventions

Stereotactic Radiosurgery RADIATION

Stereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care

Also known as: Gamma Knife

Dose Escalation (18Gy); Dose Escalation (20Gy); Dose Escalation (22Gy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northwell Health Brain Tumor Center

Lake Success, New York, 11042, United States

Location

Related Publications (5)

• Lee JH, Lee JE, Kahng JY, Kim SH, Park JS, Yoon SJ, Um JY, Kim WK, Lee JK, Park J, Kim EH, Lee JH, Lee JH, Chung WS, Ju YS, Park SH, Chang JH, Kang SG, Lee JH. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature. 2018 Aug;560(7717):243-247. doi: 10.1038/s41586-018-0389-3. Epub 2018 Aug 1.

  PMID: 30069053 BACKGROUND

• Piccirillo SG, Spiteri I, Sottoriva A, Touloumis A, Ber S, Price SJ, Heywood R, Francis NJ, Howarth KD, Collins VP, Venkitaraman AR, Curtis C, Marioni JC, Tavare S, Watts C. Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. Cancer Res. 2015 Jan 1;75(1):194-202. doi: 10.1158/0008-5472.CAN-13-3131. Epub 2014 Nov 18.

  PMID: 25406193 BACKGROUND

• Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006 Dec 7;444(7120):756-60. doi: 10.1038/nature05236. Epub 2006 Oct 18.

  PMID: 17051156 BACKGROUND

• Chen L, Guerrero-Cazares H, Ye X, Ford E, McNutt T, Kleinberg L, Lim M, Chaichana K, Quinones-Hinojosa A, Redmond K. Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):616-22. doi: 10.1016/j.ijrobp.2013.02.014. Epub 2013 Mar 26.

  PMID: 23540348 BACKGROUND

• Ogura K, Mizowaki T, Arakawa Y, Ogura M, Sakanaka K, Miyamoto S, Hiraoka M. Initial and cumulative recurrence patterns of glioblastoma after temozolomide-based chemoradiotherapy and salvage treatment: a retrospective cohort study in a single institution. Radiat Oncol. 2013 Apr 23;8:97. doi: 10.1186/1748-717X-8-97.

  PMID: 24499582 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Glioma; Lymphoma, Follicular

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alexis M Demopoulos, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 21, 2019
• Study Start: December 24, 2018
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: March 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)