This phase I trial studies the best dose and side effects of ruxolitinib when given together with radiation therapy with or without temozolomide, and to see how well they work in treating patients with newly diagnosed grade III glioma or glioblastoma. Ruxolitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Temozolomide works by damaging the deoxyribonucleic acid (DNA) of tumor cells so that they cannot divide properly. Giving ruxolitinib and radiation therapy with or without temozolomide may work better in treating patients with grade III glioma or glioblastoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03514069.
PRIMARY OBJECTIVES:
I. To determine maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) in patients with unmethylated MGMT high-grade glioma (HGG) (ARM I).
II. To determine maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) and daily temozolomide (TMZ) at 75 mg/m^2 in patients with methylated MGMT high-grade glioma (HGG) (ARM II).
SECONDARY OBJECTIVES:
I. Safety of combination of ruxolitinib with radiation (ARM I).
II. Progression free survival (PFS) (ARM I&II).
III. Overall survival (OS) (ARM I&II).
IV. Safety of combination of ruxolitinib with radiation and temozolomide (ARM II).
EXPLORATORY OBJECTIVES:
I. To evaluate whether baseline values or subsequent changes in circulating immunologic parameters and additional blood based biomarkers (including but not limited to the number of T, B and natural killer [NK] cells; the number of T cell subsets; soluble circulating cytokines) are associated with outcome.
II. To assess the perfusion and diffusion base imaging to correlate with changes and response to therapy.
III. To evaluate whether genomic profiling are associated with outcome.
OUTLINE: This is a dose escalation study of ruxolitinib. Patients are assigned to 1 of 2 arms.
ARM I: Patients with unmethylated MGMT glioblastoma and grade III glioma receive ruxolitinib orally (PO) twice daily (BID) and undergo radiation therapy (RT) 5 days a week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients with methylated MGMT glioblastoma grade III glioma receive ruxolitinib and undergo RT as in Arm I. Patients also receive temozolomide PO once daily (QD) for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 2-3 months for 1 year.
Lead OrganizationCase Comprehensive Cancer Center
Principal InvestigatorDavid Marc Peereboom
