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

NCT04574856 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: UMCC 2020.033HUM00179427
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 12-month overall survival rate

  12-month overall survival rate of study participants (failure defined as death due to any cause)

  12 months post radiation therapy (RT)

Secondary Outcomes (8)

• Overall survival

  2 years

• Progression-free survival rate

  2 years

• Proportion of failures classified by relation to the high-dose radiation region

  2 years

• Advanced MRI Gross tumor volume (GTV) and its association with overall survival

  3 months post-RT

• Patient-reported quality of life (QOL) using EORTC QLQ-C30 and BN20

  Up to 12 months post-RT

Study Arms (1)

Patients with Newly Diagnosed Glioblastoma

EXPERIMENTAL

Patients will receive dose-intensified, adaptive photon radiation therapy

Radiation: Dose-Intensified Radiotherapy; Drug: Temozolomide; Drug: Adjuvant temozolomide

Interventions

Dose-Intensified Radiotherapy RADIATION

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

Patients with Newly Diagnosed Glioblastoma

Temozolomide DRUG

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

Patients with Newly Diagnosed Glioblastoma

Adjuvant temozolomide 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.

Patients with Newly Diagnosed Glioblastoma

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• 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.

  PMID: 40058709 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

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)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michelle Kim, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 5, 2020
• Study Start: November 4, 2020
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 19, 2027
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)