Ruxolitinib With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma

Inclusion criteria

• 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.
• Confirmation that patient has sufficient tissue to undergo MGMT and IDH testing, as mandated.
• Must have a Karnofsky performance status (KPS) ≥ 70% (i.e., the patient must be able to care for themself with occasional help from others).
• Adequate organ (liver and renal) and bone marrow function within 14 days before randomization. For all parameters listed below, the most recent results available must be used:
• Absolute neutrophil count (ANC) ≥ 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.
• Platelet count ≥ 100,000/mm3. Note: Platelet transfusion is not allowed within 1 week prior to registration.
• Total bilirubin (TBL) ≤ 1.5 × institutional upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Serum albumin ≥ 2.5 g/dL.
• Patients able to become pregnant: use of highly effective contraception for at least one (1) month prior to screening and agreement to use such a method. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately. Such individuals must have a negative pregnancy test.
• Patients must have no concurrent malignancy except curatively treated early-stage bladder and prostate cancer that has been completed resected, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ 3 years.

Exclusion criteria

• 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.
• Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.
• Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment.
• Patient has previously taken ruxolitinib or is allergic to components of the study drug.
• Patients using warfarin.
• Uncontrolled immunodeficiency virus infection or active tuberculosis.
• Patients with active serious infections requiring systemic therapy.
• Known Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Participants with previous positive serology results must have negative polymerase chain reaction results.
• Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, New York Heart Association (NYHA) Grade ≥2 heart failure, uncontrolled hypertension, valvular disease, pericarditis, myocardial infarction, or other thrombosis events like including pulmonary embolism or deep vein thrombosis within 6 months of screening.
• Any other serious medical/psychiatric condition, in the judgement of the investigator, that likely to interfere or limit compliance with study requirements/treatment.