Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Active, not recruiting; Phase 1

Conditions: Glioblastoma; Glioma

Treatments: Drug: ruxolitinib; Drug: temozolomide; Radiation: radiation

Study type: Interventional

Funder types: Other

Identifiers

NCT03514069

CASE3317

Details and patient eligibility

About

The purpose of this study is to test how well the drug works, safety and tolerability of an investigational drug called Ruxolitinib in gliomas and glioblastomas, when combined with standard treatment for brain cancer, temozolomide and radiation.

Ruxolitinib is an experimental drug that works by targeting proteins in cells and stops them from growing. Ruxolitinib is experimental because it is not approved by the Food and Drug Administration (FDA) for the treatment of gliomas or glioblastomas

Temozolomide works by damaging the DNA of tumor cells so that they cannot divide properly. Some tumor cells can repair that damage and therefore be resistant to temozolomide.

Full description

Primary Objective

Arm 1:

To determine Maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) in patients with unmethylated MGMT high-grade glioma (HGG)

Arm 2:

To determine Maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) and daily temozolomide at 75 mg/m2 in patients with methylated MGMT high-grade glioma (HGG)

Secondary Objective(s)

Arm 1:

• Safety of combination of ruxolitinib with radiation
• Progression free survival (PFS)
• Overall survival (OS)

Arm 2:

• Safety of combination of ruxolitinib with radiation and temozolomide
• Progression free survival (PFS)
• Overall survival (OS)

STUDY DESIGN

A phase 1 design will be used with cohorts of 3 patients treated at each dose level in both arms 1 and 2 and monitored for treatment-related toxicities. Escalation to the next dose will proceed in the absence of dose-limiting toxicities (DLTs).

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Arm 1:

• Patients must have unmethylated MGMT supratentorial high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma).

Arm 2:

• Patients must have supratentorial methylated MGMT high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma).

Both:

• Patients must have MRI or CT with contrast within 28 days prior to starting treatment.
• 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).
• Patients must have adequate blood, kidney and liver function
• Patients must be able to provide written informed consent.
• Patients and their sexual partners must agree to avoid conception while on the study due to possible risks from experimental drugs. Women will need a negative pregnancy test to be on the study
• Patients may not have any other cancers except skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago

Exclusion criteria

• Patients with other serious diseases
• Pregnant women
• Patients getting other cancer treatments
• Patients with other cancers except for localized skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago
• Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.
• Patients who have previously received other treatments for their cancers
• Patient has previously taken ruxolitinib or is allergic to components of the study drug
• Use of blood thinners
• Human immunodeficiency virus (HIV) infection
• Active hepatitis B or C infection
• Heart diseases including abnormal electrocardiogram (EKG)
• Patients unwilling or unable to follow this protocol

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

ruxolitinib + radiation x 60 Gy for 6 weeks

Experimental group

Description:

Unmethylated O6-methylguanine DNA methyltransferase (MGMT) Glioblastoma and grade III glioma Every patient gets ruxolitinib + radiation x 60 Gy for 6 weeks over 6 weeks. The dose of radiation therapy is fixed at 60 Gy over 6 weeks

Treatment:

Radiation: radiation

Drug: ruxolitinib

ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m

Experimental group

Description:

Methylated MGMT Glioblastoma and grade III glioma. Arm 2 will start once the safe dose has been established for Arm 1 for every dose level. Every patient gets ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks. The dose of radiation therapy is fixed at 60 Gy over 6 weeks (2 Gy x 30). The dose of temozolomide is 75 mg/m2 daily for 6 weeks

Treatment:

Radiation: radiation

Drug: temozolomide

Drug: ruxolitinib