Clinical Trials /

Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

NCT03514069

Description:

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.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Glioblastoma
  • Malignant Supratentorial Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma
  • Official Title: Phase I Study of Ruxolitinib With Radiation and Temozolomide in Patients With Newly Diagnosed Grade III Gliomas and Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CASE3317
  • NCT ID: NCT03514069

Conditions

  • Glioma
  • Glioblastoma

Interventions

DrugSynonymsArms
ruxolitinibruxolitinib + radiation x 60 Gy for 6 weeks
temozolomideruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m

Purpose

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.

Detailed 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).
    

Trial Arms

NameTypeDescriptionInterventions
ruxolitinib + radiation x 60 Gy for 6 weeksExperimentalUnmethylated 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
  • ruxolitinib
ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/mExperimentalMethylated 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
  • ruxolitinib
  • temozolomide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients
Time Frame:Up to 6 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of patient study specific adverse events as a measure of safety
Time Frame:Up to 8 weeks after beginning treatment
Safety Issue:
Description:Study specific adverse events are defined as any of the following events occurring during the first 8 weeks of treatment with ruxolitinib and while being given radiation/temozolomide: grade 3 or 4 low platelets, grade 4 low red blood cells, grade 4 low white blood cells lasting more than a week, fever, any non-blood related side effect of grade 3 or greater (excluding hair loss) despite treatment, grade 4 radiation-related skin changes, and any episode of noninfectious pneumonitis.
Measure:Number of patients who have experienced progression free survival as defined by the response assessment in neuro-oncology (RANO) criteria
Time Frame:Up to 6 weeks
Safety Issue:
Description:
Measure:Average time patients stayed alive on study
Time Frame:Up to 6 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • ruxolitinib
  • radiation
  • temozolomide

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