A Phase II Study of Multiparametric MR-Guided High Dose Adaptive Radiotherapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma

University of Michigan Rogel Cancer Center1 site in 1 country30 target enrollmentNovember 4, 2020

ConditionsGlioblastoma

InterventionsDose-Intensified Radiotherapy Temozolomide Adjuvant temozolomide

DrugsTemozolomide Adjuvant temozolomide

Overview

Phase: Phase 2
Intervention: Dose-Intensified Radiotherapy
Conditions: Glioblastoma
Sponsor: University of Michigan Rogel Cancer Center
Enrollment: 30
Locations: 1
Primary Endpoint: 12-month overall survival rate
Status: Active, not recruiting
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

November 4, 2020

End Date

October 1, 2026

Last Updated

6 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

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

Arms & Interventions

Patients with Newly Diagnosed Glioblastoma

Patients will receive dose-intensified, adaptive photon radiation therapy

Intervention: Dose-Intensified Radiotherapy

Patients with Newly Diagnosed Glioblastoma

Patients will receive dose-intensified, adaptive photon radiation therapy

Intervention: Temozolomide

Patients with Newly Diagnosed Glioblastoma

Patients will receive dose-intensified, adaptive photon radiation therapy

Intervention: Adjuvant temozolomide

Outcomes

Primary Outcomes

12-month overall survival rate

Time Frame: 12 months post radiation therapy (RT)

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

Secondary Outcomes

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)
Patient objective neurocognitive function(Up to 12 months post-RT)
Overall survival(2 years)
Progression-free survival rate(2 years)
Proportion of failures classified by relation to the high-dose radiation region(2 years)
Patient-reported symptom burden using MDASI-BT(Up to 12 months post-RT)
Grade 3 or higher treatment-related toxicities(12 months post-RT)