This phase II trial studies the effect of adaptive, high dose radiotherapy guided by advanced magnetic resonance imaging (MRI) techniques and temozolomide in treating patients with newly diagnosed grade IV glioma. Adaptive, dose-intensified radiation therapy delivers radiation to certain regions of the tumor that have greater activity, as identified by advanced MRI imaging. The advanced imaging used for the radiation boost is a type of MRI called diffusion weighted MRI (or “DW-MRI”) and perfusion MRI. “Dose-intensified” means that these regions of the tumor receives a higher dose of radiation, in addition to regular regions of the tumor receiving standard doses of radiation. “Adaptive” means that the treatment plan is re-evaluated and adjusted midway through the radiation schedule to ensure the radiation remains focused on the areas that continue to have greater tumor activity. Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving adaptive, high dose chemoradiation guided by advanced MRI may work better in treating patients with glioma compared to standard chemoradiation.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04574856.
PRIMARY OBJECTIVE:
I. To determine whether dose-intensified, adaptive chemoradiation based on multiparametric MRI planning improves overall survival compared with historical control standard chemoradiation.
SECONDARY OBJECTIVES:
I. To assess whether multiparametric MRI can determine early treatment response after completion of radiation therapy that is correlated with survival.
II. To estimate progression-free survival and patterns of failure in relation to values from historical control patients.
III. To assess the ability of post-treatment advanced MRI to distinguish progression from pseudoprogression.
IV. To provide descriptive data regarding health-related quality of life, symptoms, and neurocognitive function.
V. To record toxicities of dose-intensified, adaptive chemoradiotherapy.
EXPLORATORY OBJECTIVE:
I. To provide descriptive data regarding molecular and tumor mutation status, and its association with advanced MRI metrics.
OUTLINE:
Patients undergo diffusion weighted (DW) and perfusion weighted (PW)-MRI at baseline, mid-radiation therapy (between fractions 13-15) and at 3 months post-radiation therapy. Patients undergo radiation therapy once daily (QD) 5 days per week for a total of 30 fractions and receive temozolomide orally (PO) daily for 6 weeks in the absence of disease progression or unacceptable toxicity. After surgery, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of temozolomide at investigator’s discretion.
After completion of study treatment, patients are followed up at 1, 3, 7 and 12 months after radiation therapy, then periodically for up to 2 years after chemoradiation.
Lead OrganizationUniversity of Michigan Rogel Cancer Center
Principal InvestigatorMichelle Miran Kim
