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Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

Primary Purpose

Glioma, Glioblastoma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ruxolitinib

radiation

temozolomide

About this trial

This is an interventional treatment trial for Glioma focused on measuring ruxolitinib, radiation, temozolomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

ruxolitinib + radiation x 60 Gy for 6 weeks

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

Arm 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

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients

Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients

Secondary Outcome Measures

Number of patient study specific adverse events as a measure of safety

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.

Number of patients who have experienced progression free survival as defined by the response assessment in neuro-oncology (RANO) criteria

Average time patients stayed alive on study

Full Information

NCT ID

NCT03514069

First Posted

April 20, 2018

Last Updated

August 16, 2023

Sponsor

Case Comprehensive Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT03514069

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 5, 2018 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioma, Glioblastoma

Keywords

ruxolitinib, radiation, temozolomide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ruxolitinib + radiation x 60 Gy for 6 weeks

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ruxolitinib

Intervention Description

Starting dose ruxolitinib 10 mg twice daily

Intervention Type

Radiation

Intervention Name(s)

radiation

Intervention Description

60gy for 6 weeks

Intervention Type

Drug

Intervention Name(s)

temozolomide

Intervention Description

75mg/m2

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients

Time Frame

Up to 6 weeks

Title

Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients

Time Frame

Up to 6 weeks

Secondary Outcome Measure Information:

Title

Number of patient study specific adverse events as a measure of safety

Description

Time Frame

Up to 8 weeks after beginning treatment

Title

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

Title

Average time patients stayed alive on study

Time Frame

Up to 6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Peereboom, MD

Organizational Affiliation

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

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Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

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