GlioblastomaNCT03956706
Study of Stereotactic Radiosurgery to the Subventricular Zone in Malignant Gliomas
A study testing Stereotactic Radiosurgery in people with Glioblastoma and Astrocytoma, Grade III, run by Northwell Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Astrocytoma, Grade III, Astrocytoma, Grade IV
- What is being tested?
- Stereotactic Radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Dec 2018to 1 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwell Health Brain Tumor Center
Lake Success, New York, 11042
About this study
Official title: 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.
Read the 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.
- Being tested
- Stereotactic Radiosurgery
- Keywords
- SRS, Stereotactic Radiosurgery, Glioblastoma, Astrocytoma, Grade III, Grade IV, Glioma, Malignant Glioma, Gamma Knife
- Medical subject headings
- Glioblastoma, Astrocytoma, Glioma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic RadiosurgeryRadiation
Also called Gamma Knife
Stereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (18Gy) | Experimental | Receive additional dose of 18Gy to the subventricular zone Receives: Radiation: Stereotactic Radiosurgery |
| Dose Escalation (20Gy) | Experimental | Receive additional dose of 20Gy to the subventricular zone Receives: Radiation: Stereotactic Radiosurgery |
| Dose Escalation (22Gy) | Experimental | Receive additional dose of 22Gy to the subventricular zone Receives: Radiation: Stereotactic Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity of Therapy
INCIDENCE OF TREATMENT-EMERGENT ADVERSE EVENTS AS DEFINED BY CTCAE criteria as well as BY steroid requirement
Measured: 24 months
Secondary outcomes (1)
Progression-free survival
PFS measured by time to recurrence as well as pattern of recurrence
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2019
- Study start24 Dec 2018
- Primary completion1 Sep 2022
- Study completion1 Sep 2022
Why it stopped: no partipants enrolled and investigator left the institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexis M Demopoulos, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03956706
- Sponsor's protocol ID
- 18-0794
- Status last verified
- Mar 2023
- First submitted
- 14 May 2019
- Last updated
- 15 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 30069053Piccirillo 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.
PubMed 25406193Bao 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.
PubMed 17051156Chen 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.
PubMed 23540348Ogura 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.
PubMed 24499582
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03956706
- Acronym / sponsor ID
- 18-0794
- Keywords
- SRS, Stereotactic Radiosurgery, Glioblastoma, Astrocytoma, Grade III, Grade IV, Glioma, Malignant Glioma
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no partipants enrolled and investigator left the institution
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 24 Dec 2018 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 1 Sep 2022 (actual)
- First posted
- 21 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation (18Gy) | Experimental | Radiation: Stereotactic RadiosurgeryReceive additional dose of 18Gy to the subventricular zone |
| Dose Escalation (20Gy) | Experimental | Radiation: Stereotactic RadiosurgeryReceive additional dose of 20Gy to the subventricular zone |
| Dose Escalation (22Gy) | Experimental | Radiation: Stereotactic RadiosurgeryReceive additional dose of 22Gy to the subventricular zone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic RadiosurgeryAlso: Gamma KnifeStereotactic radiosurgery dose escalation by either 18, 20, or 22 Gy to the subventricular zone in addition to standard of care | Radiation | Dose Escalation (18Gy), Dose Escalation (20Gy), Dose Escalation (22Gy) |
Primary outcome
Toxicity of Therapy
Time frame: 24 months
INCIDENCE OF TREATMENT-EMERGENT ADVERSE EVENTS AS DEFINED BY CTCAE criteria as well as BY steroid requirement
1 secondary outcome
Progression-free survival
Time frame: 24 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
- Background: PubMed 30069053Lee 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.
- Background: PubMed 25406193Piccirillo 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.
- Background: PubMed 17051156Bao 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.
- Background: PubMed 23540348Chen 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.
- Background: PubMed 24499582Ogura 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexis M Demopoulos, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Radiosurgery in people with Glioblastoma and Astrocytoma, Grade III, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity of Therapy (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03956706, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2023.