Spectroscopic MRI-Guided Radiation Therapy Planning in Glioblastoma

NCT ID: NCT03137888

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-20
• Study Completion Date: 2024-09-09

Brief 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.

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

Glioblastoma; Gliosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dose-Escalated Radiation Therapy

Intervention Type: RADIATION

Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks

Spectroscopic Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Patients will undergo sMRI scans within a 14 day window prior to starting treatment

Temozolomide

Intervention Type: DRUG

Given PO

Interventions

Dose-Escalated Radiation Therapy

Undergo sMRI-guided radiation therapy, dose painted to maximum of 75 Gy over six weeks

Intervention Type: RADIATION

Spectroscopic Magnetic Resonance Imaging

Patients will undergo sMRI scans within a 14 day window prior to starting treatment

Intervention Type: PROCEDURE

Temozolomide

Given PO

Intervention Type: DRUG

Other Intervention Names

RT; Radiation Therapy; sMRI; MRSI; Magnetic Resonance Spectroscopic Imaging; Methazolastone; Temcad; Temodal; Temodar; Temomedac; TMZ

Eligibility Criteria

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

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Hui-Kuo Shu

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hui-Kuo Shu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University/Winship Cancer Institute

Locations

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37218946 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32548285 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30854456 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2017-00424

Identifier Type: REGISTRY

Identifier Source: secondary_id

RAD3383-17

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA214557

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00094188

Identifier Type: -

Identifier Source: org_study_id