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Ruxolitinib and Radiation Therapy with or without Temozolomide in Treating Patients with Newly Diagnosed Grade III Glioma or Glioblastoma

Trial Status: Active

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.

Inclusion Criteria

  • ARM I: Patients must have histologically proven unmethylated MGMT supratentorial high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma)
  • ARM II: Patients must have histologically proven supratentorial methylated MGMT high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma)
  • ARM I&II: Patients must have gadolinium magnetic resonance imaging (MRI) or contrast computed tomography (CT) with contrast within 28 days prior to starting treatment
  • ARM I&II: Patients must have a Karnofsky performance status >= 70% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • ARM I&II: Absolute neutrophil count (ANC) > 1500/mm^3
  • ARM I&II: Platelets > 100,000/mm^3
  • ARM I&II: Creatinine =< 1.7 mg/dl
  • ARM I&II: Total bilirubin =< 1.5 mg/dl
  • ARM I&II: Transaminases =< 3 times above the upper limits of the institutional normal
  • ARM I&II: Patients must be able to provide written informed consent
  • ARM I&II: Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of child-bearing potential (women who are not free from menses for > 2 years, post-hysterectomy/oophorectomy, or surgically sterilized) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug as well as the standard drug (temozolomide) may be harmful to the developing fetus or nursing infant
  • ARM I&II: 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 with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
  • 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 tumor (i.e. chemotherapeutics or investigational agents).
  • 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
  • Patient is using warfarin or any other Coumadin-derivative anticoagulant or vitamin K antagonists or any form of anticoagulation including low molecular weight heparin
  • Known human immunodeficiency virus (HIV) infection
  • 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. Previous test results obtained as part of standard of care (i.e., hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with previous positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment
  • Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening
  • Pregnant or breast-feeding women
  • Patients unwilling or unable to comply with the protocol

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ACTIVE
Contact: Manmeet Singh Ahluwalia
Phone: 216-445-6145

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.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Manmeet Singh Ahluwalia

  • Primary ID CASE3317
  • Secondary IDs NCI-2018-01262
  • Clinicaltrials.gov ID NCT03514069