The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.
Provision of signed informed consent form.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Individuals of any sex, gender, race, or ethnicity ≥ 18 years of age.
Histologically confirmed glioblastoma as defined by the World Health Organization (WHO) 2021 Criteria (IDH-wildtype) that is either methylated, unmethylated, or indeterminate MGMT.
Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant.
Patients receiving concurrent therapy for their brain tumor (e.g., chemotherapeutics or investigational agents).
Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study.
Patient has previously taken ruxolitinib or is allergic to any components of the study drug.
Parallel
Ruxolitinib
Drug"During Radiation Therapy" phase: 20 mg ruxolitinib will be self-administered orally (PO) twice every day (BID), starting on Day 1 for 6 weeks. Then there will be a 4-week break after radiotherapy is complete. "Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Ruxolitinib 20 mg will be self-administered PO BID, starting on Day 1 in consecutive 28-day cycles. Either phase: Aside from the 30-day break, ruxolitinib will be continued daily until disease progression or treatment intolerance. Ruxolitinib should be administered at approximately the same time each day. The tablets should be swallowed whole with water and should not be opened, broken, or chewed. The dose may be reduced in the case of certain adverse events.
Temozolomide
Drug"During Radiation Therapy" phase: 75 mg/m\^2 will be self-administered PO once every day, starting on Day 1, for 6 weeks. Then there will be a 4-week break after radiotherapy is complete. "Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Temozolomide 150-200 mg/m\^2 will be self-administered PO BID, starting on Day 1 to Day 5 of each cycle for six cycles. Either phase: The dose may be reduced in the case of certain adverse events.
Radiation Therapy
RadiationRadiation will be administered every weekday (Monday to Friday) in 2 Gy fractions for 30 fractions during a 6-week period (60 Gy total).
Overall survival (OS) at end of study
OS is defined as the time from first treatment until the date of death from any cause at the end of the study. Participants who are lost to follow-up will be censored at the time of the last follow-up.
OS at 12 months
OS is defined as the time from first treatment until the date of death from any cause at 12 months. Participants who are lost to follow-up will be censored at the time of the last follow-up.
Progression-free survival (PFS) at 6 months
PFS is defined as the time from treatment to the first progressive disease (PD) using Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria or death due to any cause, whichever occurs first by 6 months. Participants lost to follow-up will be censored at the last follow-up. PD is defined as any of the following: * ≥ 25% increase in sum of products of perpendicular diameters or ≥ 40% increase in total volume of enhancing lesions compared to the smallest tumor measurement obtained at baseline or best response and sustained for at least 4 weeks * Any new measurable (\> 10mm × 10mm) enhancing lesions if baseline or best response demonstrated no measurable enhancing disease * Appearance of definite leptomeningeal disease * Unequivocal progression of existing non-target lesions * Clear clinical deterioration not attributable to decreased corticosteroid dose or other causes apart from tumor * Failure to return for evaluation due to death or deteriorating condition
PFS at 12 months
PFS is defined as defined as the time from treatment to the first documented PD using RANO 2.0 criteria or death due to any cause, whichever occurs first by 12 months. Participants who are lost to follow-up will be censored at the time of the last follow-up. PD is defined above for PFS at 6 months.
Objective response rate (ORR)
ORR is defined as the proportion of participants in the analysis population who have a complete or partial response (CR or PR) using RANO 2.0 criteria. CR is defined as the disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks, no new lesions, stable or better clinical status, and no corticosteroid use. PR is defined as 50% or more decrease in the in sum of the products of perpendicular diameters of all lesions or 65% or more decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks, no new lesions, no progression of non-measurable enhancing disease or non-target lesions, corticosteroid dose should be the same or lower compared to baseline, and clinical status should be stable or better compared to baseline.
Click on the lead sponsor to view all of their trials.
Baptist Health South Florida
Lead sponsor
Incyte Corporation
Collaborator
