CompletedNCT03137888Updated Aug 3, 2025Results posted

Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma

A Phase 2 interventional study of Dose-Escalated Radiation Therapy and Spectroscopic Magnetic Resonance Imaging in Glioblastoma and Gliosarcoma, sponsored by Emory University. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-03.

Sponsored by Emory University · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 30
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

This pilot clinical trial studies the side effects of spectroscopic magnetic resonance imaging (MRI)-guided radiation therapy and how well it works in treating patients with newly-diagnosed glioblastoma or gliosarcoma. Spectroscopic MRI can show doctors where the extent of tumor is in the brain beyond current clinical MRI scans by mapping areas of high tumor metabolism. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Spectroscopic MRI-guided radiation therapy may work better in treating patients with glioblastoma or gliosarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the feasibility of using spectroscopic MRI (sMRI) to guide dose-escalated radiation therapy (RT) for newly-diagnosed glioblastoma (GBM)s.

II. To determine the safety of using sMRI to guide dose-escalated RT for newly-diagnosed GBMs.

SECONDARY OBJECTIVE:

I. To determine whether the progression free survival at 1 year with sMRI-guided, dose-escalated RT is improved for newly-diagnosed GBMs.

TERTIARY OBJECTIVES:

I. To determine whether sMRI-guided, dose-escalated RT increases the overall survival of patients with newly diagnosed GBMs.

II. To determine whether sMRI data obtained after initiation of therapy (at 2 weeks after RT/TMZ start and prior to cycle 1 and 5 of adjuvant temozolomide [TMZ]) will provide early evidence of GBM progression not seen on standard MRIs.

III. To determine whether performance on neurocognitive and quality-of-life (QOL) assessments in newly-diagnosed GBM patients treated with sMRI-guided, dose-escalated RT differ from historical controls.

OUTLINE:

Patients undergo sMRI-guided radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide orally (PO) daily during radiation therapy for up to 42 days.

After completion of study treatment, patients are followed up every 3 months for up to 2 years and then periodically.

Conditions studied

Glioblastoma
Gliosarcoma

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Patients must have a newly-diagnosed glioblastoma or gliosarcoma that has been confirmed pathologically by a board-certified neuropathologist
Patients must be able to have MRI scans
Patients must have the following lab values ≤ 14 days prior to registration:
- White blood cell (WBC) ≥ 3,000/µL
- Absolute neutrophil count (ANC) ≥ 1,500/µL
- Platelet count of ≥ 75,000/µL
- Hemoglobin ≥ 9.0 gm/dL (transfusion is allowed to reach minimum level)
- Serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.0 x upper limit of normal (ULN)
- Bilirubin ≤ 2 x ULN
- Creatinine ≤ 1.5 mg/dL
Patients must have a life expectancy of ≥ 12 weeks
Patients must have a Karnofsky performance status (KPS) ≥ 60
Patients who are women of childbearing potential must have a negative pregnancy test documented ≤ 14 days prior to registration; this is not specific to dose escalation and is mandatory for standard care for patients being treated with radiation therapy; the cost of this test will be covered by standard of care
Patients must be able to understand and provide written informed consent
Members of all races and ethnic groups are eligible for this trial; subjects will be approximately representative of the demographics of the referral base for the participating institutions
Patient must be able to swallow capsules
Patients must be willing to forego other cytotoxic and non-cytotoxic therapies against the tumor while being treated on this protocol

Exclusion criteria

Exclusion Criteria:

Patients with pacemakers, aneurysm clips, neurostimulators, cochlear implants, metal in ocular structures, history of being a steel worker, or other incompatible implants which makes MRI safety an issue are excluded
Patients that have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy are excluded
Patients with a history of any other invasive cancer (except non-melanoma skin cancer and excluding carcinoma in-situ), unless in complete remission and off of all therapy for that disease for ≥ 3 years, are ineligible
Patients with an active infection or serious intercurrent medical illness are ineligible
Patients receiving any other investigational agents are excluded
Patients who have received prior cytotoxic, non-cytotoxic or experimental drug therapies for brain tumor are excluded
Patients with a history of prior cranial radiation are ineligible
Patients may not be enrolled on any other therapeutic trial for which they are receiving an anti-tumor therapy
Patients with GBMs located in the following anatomical regions known to have magnetic susceptibility or poor signal will be excluded: mesial temporal lobe, orbitofrontal cortex, prefrontal cortex, medial frontal gyrus, brainstem, and cerebellum
The maximum radiation target volume for gross tumor volume 3 (GTV3) is 65 cc (per NRG Oncology guide); patient may be excluded after the first sMRI scan if the GTV3 volume is greater than 65 cc (we anticipate that contrast-enhancing tumor volume [residual tumor volume following tumor resection] would be less than 20 cc)

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 30 participants (actual)

Study arms

Experimental
sMRI-Guided RT with TMZ
Patients undergo spectroscopic magnetic resonance imaging-guided dose-escalated radiation therapy daily for the first 5 days of every week (Monday - Friday) over 6 weeks. Patients also receive standard of care temozolomide PO daily during radiation therapy for up to 42 days.
Radiation: Dose-Escalated Radiation Therapy · Procedure: Spectroscopic Magnetic Resonance Imaging · Drug: Temozolomide

Interventions

RadiationDose-Escalated Radiation Therapy
Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks
Also known as: RT, Radiation Therapy
ProcedureSpectroscopic Magnetic Resonance Imaging
Patients will undergo sMRI scans within a 14 day window prior to starting treatment
Also known as: sMRI, MRSI, Magnetic Resonance Spectroscopic Imaging
DrugTemozolomide
Given PO
Also known as: Methazolastone, Temcad, Temodal, Temodar, Temomedac, TMZ

What researchers measure

Primary outcomes

Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform
Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment.
Time frame: Up to 2 years after completion of therapy
Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0
The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT.
Time frame: Up to 2 years after completion of therapy

Secondary outcomes

Progression Free Survival (PFS)
Patients were followed at least every 3 months for 2 years from the start of RT.
Time frame: 2 years from the start of RT.

Other outcomes

Overall Survival (OS)
Patients were followed at least every 3 months for 2.5 years from the start of RT.
Time frame: 2.5 years from start of RT

Results

Posted Aug 3, 2025

Participant flow

Participant flow — Overall Study
Milestone	sMRI-Guided RT With TMZ
Started	30
Completed	30
Not completed	0

Outcome measures

PrimaryFeasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform

Feasibility of this approach will be determined by whether treatment volumes based on sMRI can be co-registered with clinical images and transferred into the radiation treatment execution platform in a seamless manner, so that sMRI information can be efficiently applied to the patient treatment.

Time frame:: Up to 2 years after completion of therapy
Reported as:: Count of participants · Participants

Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform
Participants	sMRI-Guided RT With TMZ
Feasibility as Assessed by Successful Co-registration of sMRI-based Treatment Volumes With Clinical Images Into the Radiation Treatment Execution Platform	30

PrimaryIncidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0

The safety of sMRI to guide dose-escalated RT will be confirmed by assessing toxicity potentially attributable to the RT.

Time frame:: Up to 2 years after completion of therapy
Reported as:: Number · Adverse Events

Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0
Adverse Events	sMRI-Guided RT With TMZ
Incidence of Adverse Event Assessed by Common Terminology Criteria for Adverse Events Version 4.0	79 (62 to 99)

SecondaryProgression Free Survival (PFS)

Patients were followed at least every 3 months for 2 years from the start of RT.

Time frame:: 2 years from the start of RT.
Reported as:: Median · Months

Progression Free Survival (PFS)
Months	sMRI-Guided RT With TMZ
Progression Free Survival (PFS)	16.6 (11.6 to 24.0)

Other pre-specifiedOverall Survival (OS)

Patients were followed at least every 3 months for 2.5 years from the start of RT.

Time frame:: 2.5 years from start of RT
Reported as:: Median · Months

Overall Survival (OS)
Months	sMRI-Guided RT With TMZ
Overall Survival (OS)	23 (18.6 to 27.3)

Adverse events

Collected over Up to 2 years after completion of therapy. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
sMRI-Guided RT With TMZ	16/30 (53.3%)	14/30 (46.7%)	30/30 (100%)

Most frequent serious events

Most frequent serious events
Event	sMRI-Guided RT With TMZ
ThrombocytopeniaBlood and lymphatic system disorders	5/30
Muscle weaknessMusculoskeletal and connective tissue disorders	2/30
NeutropeniaImmune system disorders	1/30
TransaminitisBlood and lymphatic system disorders	1/30
HypokalemiaMetabolism and nutrition disorders	1/30
EdemaGeneral disorders	1/30
FatigueGeneral disorders	1/30
HeadachesNervous system disorders	1/30
Leg edemaGeneral disorders	1/30

Most frequent other events

Showing 10 of 78

Most frequent other events
Event	sMRI-Guided RT With TMZ
FatigueGeneral disorders	28/30
General disorders and administration site conditionsGeneral disorders	19/30
ConstipationGastrointestinal disorders	16/30
SeizureNervous system disorders	15/30
AlopeciaSkin and subcutaneous tissue disorders	14/30
HeadacheNervous system disorders	14/30
Nervous system disordersNervous system disorders	13/30
AnorexiaMetabolism and nutrition disorders	12/30
Blood and lymphatic system disorders - Other, specifyBlood and lymphatic system disorders	12/30
NauseaGastrointestinal disorders	11/30

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	sMRI-Guided RT With TMZ
<=18 years	0
Between 18 and 65 years	23
>=65 years	7

Age, Continuous
Age, Continuous(Years)	sMRI-Guided RT With TMZ
Mean	56.4 (20.8 to 71.6)

Sex: Female, Male
Sex: Female, Male(Participants)	sMRI-Guided RT With TMZ
Female	11
Male	19

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	sMRI-Guided RT With TMZ
American Indian or Alaska Native	0
Asian	1
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	28
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(Participants)	sMRI-Guided RT With TMZ
United States	30

Study locations

3 sites

University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia 30322, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287, United States

References and documents

Publications

Trivedi AG, Kim SH, Ramesh KK, Giuffrida AS, Weinberg BD, Mellon EA, Kleinberg LR, Barker PB, Han H, Shu HG, Shim H, Schreibmann E. Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma. Tomography. 2023 May 21;9(3):1052-1061. doi: 10.3390/tomography9030086. PubMed 37218946 ↗
Ramesh K, Gurbani SS, Mellon EA, Huang V, Goryawala M, Barker PB, Kleinberg L, Shu HG, Shim H, Weinberg BD. The Longitudinal Imaging Tracker (BrICS-LIT):A Cloud Platform for Monitoring Treatment Response in Glioblastoma Patients. Tomography. 2020 Jun;6(2):93-100. doi: 10.18383/j.tom.2020.00001. PubMed 32548285 ↗
Gurbani S, Weinberg B, Cooper L, Mellon E, Schreibmann E, Sheriff S, Maudsley A, Goryawala M, Shu HK, Shim H. The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow. Tomography. 2019 Mar;5(1):184-191. doi: 10.18383/j.tom.2018.00028. PubMed 30854456 ↗

Study documents

Protocol and statistical analysis plan · Sep 15, 2020
Informed consent form · Mar 13, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03137888
Lead sponsor: Emory University
Collaborators: Johns Hopkins University, University of Miami, National Cancer Institute (NCI), National Institutes of Health (NIH)
Responsible party: Hui-Kuo Shu (Principal Investigator, Emory University) — Principal investigator
First posted: May 3, 2017
Start date: Sep 20, 2017
Primary completion: Sep 9, 2024
Completion: Sep 9, 2024
Results posted: Aug 3, 2025
Last update: Aug 3, 2025

Study contacts

Hui-Kuo Shu, MD, PhD

principal investigator · Emory University/Winship Cancer Institute

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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