Integrating Biology for Safe Intensification of Glioblastoma Hypofractionated Treatment on the MR-Linac (INSIGHT MRL)

INSIGHT MRL: INtegrating Biology for Safe Intensification of Glioblastoma Hypofractionated Treatment on the MR-Linac

This is a phase 1 study to examine the safety and tolerability of biology-guided dose intensified hypofractionated radiation therapy (RT) using MR-Linac for patients with high grade glioma (HGG). Investigators will enroll 20 patients with Grade 3 or 4, IDH wild-type (IDHwt), HGG. Intraoperative assessment of residual tumor burden will be performed at 6 surgical margins (anterior, posterior, superior, inferior, medial, lateral) using FastGlioma. Each margin will be graded on a scale of 0 to 3, with 0 being no tumor, 1 atypical cell, 2 sparse tumor infiltration, and 3 dense tumor infiltration.

Study Overview

• Status: Not yet recruiting
• Conditions: High-grade Glioma
• Intervention / Treatment: Device: MR-Linac System; Radiation: Radiation Therapy; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cancer Trials Inbox; Email: CancerTrials@nyulangone.org
• Study Contact Backup: Name: Jonathan Yang, MD, PhD; Phone Number: 2127316030; Email: CancerTrials@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants male or female of age 18 or older
• Ability to understand and the willingness to sign a written informed consent document
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Have histologically confirmed, newly diagnosed high grade glioma (histologic grade 3 or 4, IDH wildtype)
• Must have completed surgery with FastGlioma
• Patients can either be consented before or after surgery. Patients can be a maximum of 6 weeks post-surgery period to the start of MRL-RT.
• Ability to undergo radiotherapy with an MR-Linac machine including effective immobilization for the duration of treatment and required MR sequences
• Subjects must have adequate bone marrow, liver and kidney function defined as:
• Hemoglobin >/= 9.0 g/dL
• Absolute neutrophil count >/= 1.5 x 109/L
• Platelet count >/= 100 x 109/L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 x ULN
• Creatinine within normal limits OR measured creatinine clearance (CL) >50 mL/min OR calculated creatinine clearance (CL) >50 mL/min as determined by Cockcroft-Gault
• Men who partner with a woman of childbearing potential must agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable or barrier method) while on study and for 4 months afterward.
• For Female participants:
• While on study treatment a participant must not breastfeed or be pregnant
• Have a negative highly sensitive (eg, beta-human chorionic gonadotropin [β-hCG]) pregnancy test at screening and agree to further pregnancy tests per the protocol.
• Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used.
• Female participants (pre- or perimenopausal) must use the appropriate highly effective, contraception method within 28 days of the first dose of study treatment.

Exclusion Criteria:

• Uncontrolled intercurrent illness
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments of the investigational regimen. Patients whose prior or concurrent malignancy natural history and/or treatment does NOT have the potential to impact safety or study assessments are eligible.
• Any unresolved toxicity NCI Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from a previous anticancer therapy, with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment may be included after consultation with the study PI.
• Prior evidence of IDH mutation by IHC or DNA sequencing (i.e., IDH wild type only)
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Subject is pregnant or planning to become pregnant or nursing (lactating).
• Subject is enrolled in another investigational trial and/or is taking investigational medication and/or has been treated with an investigational device </= 30 days prior to planned procedure date.
• Contraindications to MRI examination as per standard MRI screening policy
• Contraindication to Gadolinium-based contrast media
• Inability to lie flat in a supine position for at least 30 minutes
• Inability to tolerate immobilization in a head thermoplastic mask
• Prior therapeutic cranial irradiation
• Leptomeningeal dissemination of disease
• Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MRL-RT + Temozolomide; Participants will undergo Magnetic Resonance (MR)-Linac Radiation Therapy (MRL-RT), which involves planning radiation therapy using an MR-Linear Accelerator (Linac) system. Participants will receive radiation over a period of 3 weeks; concurrent Temozolomide (75 mg/m2) will administered daily throughout the 3 weeks of treatments and stopped on the final day of RT.

Device: MR-Linac System; Elekta Unity is an MR-Linac with continuous, anatomy-specific MR imaging and comprehensive motion management for precision radiation therapy.; Other Names: Elekta Unity; Radiation: Radiation Therapy; Radiation therapy will be delivered twice a week on non-consecutive days for three weeks.; Drug: Temozolomide; Temozolomide (75 mg/m2) is administered daily throughout the 3 weeks of treatments and stopped on the final day of radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Occurrence of Dose-Limiting Toxicities	Measure of safety and tolerability.	Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS defined as time from start of radiation treatment to first documented disease progression or death due to any cause.	Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)
Overall Survival (OS)	OS is defined as time from the start of treatment until death from any cause.	Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Jonathan Yang, MD, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Azoles; Dacarbazine; Triazenes; Imidazoles; Temozolomide; Radiotherapy
• Other Study ID Numbers: 25-01305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset will be shared upon reasonable request beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Jonathan.Yang@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Jonathan.Yang@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No