Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma

NCT ID: NCT04574856

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-04
• Study Completion Date: 2026-10-31

Brief Summary

This study will investigate whether or not intensified radiation therapy adapted during the radiation treatment course to high-risk, treatment-resistant tumor regions will improve overall survival in patients with newly diagnosed glioblastoma (GBM) compared to conventional chemoradiotherapy.

Conditions

Glioblastoma

Study Design

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

Study Groups

Patients with Newly Diagnosed Glioblastoma

Patients will receive dose-intensified, adaptive photon radiation therapy

Group Type: EXPERIMENTAL

Dose-Intensified Radiotherapy

Intervention Type: RADIATION

Adaptive, dose-intensified radiotherapy targeting an advanced imaging signature, with a target, nominal radiotherapy dose of 80 Gy.

Temozolomide

Intervention Type: DRUG

Temozolomide chemotherapy (75 mg/m2 daily for 6 weeks)

Adjuvant temozolomide

Intervention Type: DRUG

Adjuvant temozolomide will be delivered at 150-200 mg/m2 days 1-5 every 28 days for 6 cycles, with additional cycles delivered at the discretion of the investigator.

Interventions

Dose-Intensified Radiotherapy

Adaptive, dose-intensified radiotherapy targeting an advanced imaging signature, with a target, nominal radiotherapy dose of 80 Gy.

Intervention Type: RADIATION

Temozolomide

Temozolomide chemotherapy (75 mg/m2 daily for 6 weeks)

Intervention Type: DRUG

Adjuvant temozolomide

Adjuvant temozolomide will be delivered at 150-200 mg/m2 days 1-5 every 28 days for 6 cycles, with additional cycles delivered at the discretion of the investigator.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Newly diagnosed, histologically-confirmed supratentorial WHO grade IV gliomas including glioblastoma (all variants) and gliosarcoma. Prior low-grade glioma without prior RT, now with malignant progression are eligible.
• Karnofsky performance status >=70
• Minimal life expectancy of 12 weeks
• Adequate bone marrow reserve (Hemoglobin ≥ 10 g/dL, absolute neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3), acceptable liver function (total bilirubin ≤ 2 x upper limit of normal (ULN) (unless elevated bilirubin is related to Gilbert syndrome), and ALT/AST ≤ 5 x ULN) and renal function (serum creatinine ≤ 2.0 mg/dL) within 14 day prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
• Maximal contiguous diameter of tumor based on high b-value diffusion MRI and DCE perfusion MRI ≤5 cm
• Patients must be registered within 6 weeks of most recent resection
• Females of child-bearing potential must have a negative pregnancy test within 14 days prior to registration. Patients with reproductive potential must agree to use an effective contraceptive method during treatment and study participation.

Exclusion Criteria

• Recurrent glioma, or tumor involving the brainstem or cerebellum
• Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment is not permitted. Prior chemotherapy for a different cancer is allowable if interval since last treatment cycle completion is >3 years.
• Evidence of CSF dissemination (positive CSF cytology for malignancy or MRI findings consistent with CSF dissemination)
• Evidence of severe concurrent disease requiring treatment
• Prior invasive malignancy (except non-melanoma skin cancer or non-life limiting invasive malignancy that may not require treatment, such as low-risk prostate cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of breast, oral cavity or cervix are all permissible)
• Patients unable to undergo MRI exams (i.e. patients with non-compatible devices such as cardiac pacemakers, other implanted electronic devices, metallic prostheses, or ferromagnetic prostheses [e.g. pins in artificial joints and surgical pins/clips], or unable to receive gadolinium for MRI, as per the standard Department of Radiology MRI screening criteria)
• Patients treated with previous cranial or head/neck radiotherapy leading to significant radiation field overlap as determined by treating physician
• Multifocal disease (>1 lobe of involvement) of discontiguous contrast enhancing disease as seen on conventional MRI
• Pregnancy or lactation

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

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Kim, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Countries

United States

References

Kim MM, Aryal MP, Suresh K, Rosen BS, Parmar H, You D, Leung D, Clarke N, Fortunato J, Al-Holou W, Heth J, Altshuler D, Hollon T, Edwards DM, Wahl DR, Lawrence TS, Cao Y. A Phase 2 Study of Multiparametric Magnetic Resonance Imaging-Guided High-Dose Response-Adaptive Radiation Therapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma: Results From an Interim Analysis. Int J Radiat Oncol Biol Phys. 2025 Jul 1;122(3):605-610. doi: 10.1016/j.ijrobp.2025.02.020. Epub 2025 Mar 8.

Reference Type: DERIVED

PMID: 40058709 (View on PubMed)

Other Identifiers

HUM00179427

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2020.033

Identifier Type: -

Identifier Source: org_study_id