Hypoxia-targeted Radiotherapy Boost for GBM

NCT07769918 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 25-01439
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the use of dynamic contrast-enhanced MRI (DSC-MRI) to identify and target hypoxic tumor regions in glioblastoma (GBM). The study is divided into two phases: Phase 1 will focus on biologic validation in newly diagnosed GBM patients, while Phase 2 will assess the clinical implementation of DSC-MRI-guided radiotherapy in recurrent or postoperative GBM patients. The primary endpoints are the validation of DSC-MRI in identifying hypoxic regions and assessing the safety and efficacy of radiation therapy based on these findings.

Conditions

Glioblastoma (GBM)

Outcome Measures

Primary Outcomes (3)

• Proportion of participants with successful acquisition and processing of interpretable hypoxia maps

  Up to 3 months

• Proportion of participants in whom DSC-MRI hypoxia maps are successfully incorporated into radiotherapy planning and the hypoxia-targeted boost is delivered while meeting organ-at-risk constraints.

  Up to 3 months

• Incidence of treatment-related toxicities

  According to CTCAE v6.0, with particular focus on Grade ≥3 treatment-related toxicities.

  Up to 3 months

Secondary Outcomes (2)

• Progression-free survival (PFS)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

Study Arms (2)

Phase 1: Biologic Validation Cohort

EXPERIMENTAL

Participants with newly diagnosed, resectable GBM will undergo pre-operative DSC-MRI to generate individualized hypoxia maps. Intra-operative neuro-navigation will guide paired sampling of hypoxic and normoxic regions for spatial transcriptomic analysis and IHC to validate DSC-MRI findings.

Device: Dynamic susceptibility contrast MRI (DSC-MRI); Other: Cercare Medical Neurosuite (CMN) DSC-MRI-derived hypoxia maps; Radiation: Varian TrueBeam

Phase 2: Clinical Implementation Cohort

EXPERIMENTAL

Participants with postoperative or recurrent GBM will receive DSC-MRI-informed radiotherapy, including a targeted radiation boost to hypoxic subvolumes while maintaining standard dose constraints for organs at risk. Standard-of-care MRI will be performed before and after radiotherapy, with an optional mid-treatment DSC-MRI to assess hypoxia dynamics and support adaptive radiation planning.

Device: Dynamic susceptibility contrast MRI (DSC-MRI); Other: Cercare Medical Neurosuite (CMN) DSC-MRI-derived hypoxia maps; Radiation: Varian TrueBeam

Interventions

Dynamic susceptibility contrast MRI (DSC-MRI) DEVICE

Non-invasively characterize tumor perfusion and derive imaging surrogates of hypoxia that inform tissue sampling (Phase 1) and radiotherapy planning (Phase 2). DSC-MRI is an advanced perfusion technique that acquires rapid, repeated gradient-echo echo-planar images during intravenous administration of a gadolinium-based contrast agent which will aid in the generation of parametric maps.

Phase 1: Biologic Validation Cohort; Phase 2: Clinical Implementation Cohort

Cercare Medical Neurosuite (CMN) DSC-MRI-derived hypoxia maps OTHER

In Phase 1, these maps will guide neuro-navigation for intra-operative sampling of imaging-defined hypoxic and normoxic subregions to enable biologic and spatial transcriptomic validation. In Phase 2, DSC-MRI-derived hypoxia maps will be rigidly co-registered to planning MRI/CT datasets and imported into the treatment planning system to define hypoxic subvolumes eligible for a conformal radiotherapy boost, delivered with contemporary inverse-planned techniques while respecting all organ-at-risk constraints and standard-of-care dose limits.

Phase 1: Biologic Validation Cohort; Phase 2: Clinical Implementation Cohort

Varian TrueBeam RADIATION

Radiotherapy will be delivered using the Varian TrueBeam system. All participants will receive dynamic susceptibility contrast (DSC)-MRI-informed radiotherapy incorporating an integrated boost to imaging-defined hypoxic tumor subvolumes. Radiotherapy will be delivered using inverse-planned intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), once daily, five fractions per week, with daily volumetric image guidance.

Phase 1: Biologic Validation Cohort; Phase 2: Clinical Implementation Cohort

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent.
• ≥18 years of age.
• All suspected GBM patients including newly diagnosed and recurrent GBM who are undergoing resection (Phase 1). Or all suspected newly diagnosed or recurrent GBM being treated with radiation where there is still visible tumor) (Phase 2)
• Participants with a history of prior malignancies and previous LITT are permitted to enroll.
• KPS \> 50.
• Subjects must have adequate liver and kidney function, defined as:
• Liver transaminase levels ≤2.5 × the upper limit of normal (ULN); total bilirubin ≤1.5 × ULN, except in subjects with Gilbert's Disease in whom total bilirubin ≤5 × ULN is allowed.
• Creatinine clearance ≥60 mL/min measured from a 24-hour urine collection or calculated based on the Cockcroft-Gault formula OR serum creatinine ≤ULN.
• Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy. Female subjects of childbearing potential who are undergoing RT or who are partners to male subjects in the study should avoid sexual activity or use a highly effective method of birth control during sexual intercourse. Acceptable, highly effective methods of birth control include intrauterine device (IUD)/intrauterine hormone releasing system (IUS), bilateral tube occlusion, vasectomized partner, combined (estrogen and progesterone containing) or progesterone-only hormonal contraceptives (oral, intravaginal, transdermal, injectable).
• Patient with recurrent tumor amendable to reirradiation and is at least 3 months from end of prior brain radiation therapy

You may not qualify if:

• Subjects must not meet any of the following criteria to be eligible for study participation:
• Subjects with bone marrow impairment as evidenced by hemoglobin \<8.0 g/dL, neutrophil count \<1.5 × 109/L, or platelets \<100 × 109/L.
• Significant cardiac conduction abnormalities, including a history of long corrected QT (QTc) interval syndrome (\>450 msec per Fridericia's formula) and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification \>2 at screening.
• Subjects who are pregnant or breast-feeding.
• Contraindication to temozolomide
• Severe headache, rapidly progressive neurologic decline, objective neurologic manifestations of uncal herniation, depressed level of consciousness

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Perfusion Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Magnetic Resonance Imaging; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Jonathan So, MD, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan So, MD, PhD

CONTACT

646-501-8900; Jonathan.So2@nyulangone.org

Study Design

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

Study Record Dates

• First Submitted: August 13, 2026
• First Posted: August 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Jonathan.so2@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.

Locations

US (1)