Integrating Biology for Safe Intensification of Glioblastoma Hypofractionated Treatment on the MR-Linac

Official title

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

Overview

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.

Interventions

• Device MR-Linac System
  Elekta Unity is an MR-Linac with continuous, anatomy-specific MR imaging and comprehensive motion management for precision radiation therapy.
• 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.

Primary outcome measures

• Overall Occurrence of Dose-Limiting Toxicities [Time frame: Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)]

Secondary outcome measures (2)

• Progression-Free Survival (PFS) [Time frame: Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)]
• Overall Survival (OS) [Time frame: Up to 1 Year Post Radiation Treatment Initiation (Up to Month 14)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• NYU Langone Health — New York

Identifiers

NCT: NCT07457307 · 25-01305

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗