Glioblastoma (GBM)
Conditions
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.
Interventions
DEVICEDynamic susceptibility contrast MRI (DSC-MRI)
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.
OTHERCercare Medical Neurosuite (CMN) DSC-MRI-derived hypoxia maps
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.
RADIATIONVarian TrueBeam
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.
Sponsors
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent. 2. ≥18 years of age. 3. 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) 4. Participants with a history of prior malignancies and previous LITT are permitted to enroll. 5. KPS \> 50. 6. Subjects must have adequate liver and kidney function, defined as: 7. 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. 8. Creatinine clearance ≥60 mL/min measured from a 24-hour urine collection or calculated based on the Cockcroft-Gault formula OR serum creatinine ≤ULN. 9. 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). 10. Patient with recurrent tumor amendable to reirradiation and is at least 3 months from end of prior brain radiation therapy
Exclusion criteria
Subjects must not meet any of the following criteria to be eligible for study participation: 1. Subjects with bone marrow impairment as evidenced by hemoglobin \<8.0 g/dL, neutrophil count \<1.5 × 109/L, or platelets \<100 × 109/L. 2. 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. 3. Subjects who are pregnant or breast-feeding. 4. Contraindication to temozolomide 5. Severe headache, rapidly progressive neurologic decline, objective neurologic manifestations of uncal herniation, depressed level of consciousness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 3 months | According to CTCAE v6.0, with particular focus on Grade ≥3 treatment-related toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to 5 years | PFS is defined as the time from initiation of hypoxia-guided radiotherapy to disease progression or death from any cause. |
| Overall survival (OS) | Up to 5 years | OS is defined as the time from initiation of hypoxia-guided radiotherapy to death from any cause. |
Countries
United States
Contacts
CONTACTJonathan So, MD, PhD
PRINCIPAL_INVESTIGATORJonathan So, MD, PhD
NYU Langone Health
Outcome results
None listed