Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03514069

Collaborator

(none)

Enrollment

Location

Arms

54.9

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Glioma Glioblastoma	Drug: ruxolitinib Radiation: radiation Drug: temozolomide	Phase 1

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of Ruxolitinib With Radiation and Temozolomide in Patients With Newly Diagnosed Grade III Gliomas and Glioblastoma

Actual Study Start Date :

Jun 5, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ruxolitinib + radiation x 60 Gy for 6 weeks 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	Drug: ruxolitinib Starting dose ruxolitinib 10 mg twice daily Radiation: radiation 60gy for 6 weeks
Experimental: ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m 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	Drug: ruxolitinib Starting dose ruxolitinib 10 mg twice daily Radiation: radiation 60gy for 6 weeks Drug: temozolomide 75mg/m2

Arm

Intervention/Treatment

Experimental: ruxolitinib + radiation x 60 Gy for 6 weeks

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

Drug: ruxolitinib

Starting dose ruxolitinib 10 mg twice daily

Radiation: radiation

60gy for 6 weeks

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

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

Drug: ruxolitinib

Starting dose ruxolitinib 10 mg twice daily

Radiation: radiation

60gy for 6 weeks

Drug: temozolomide

75mg/m2

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients [Up to 6 weeks]
Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients [Up to 6 weeks]

Secondary Outcome Measures

Number of patient study specific adverse events as a measure of safety [Up to 8 weeks after beginning treatment]
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 [Up to 6 weeks]
Average time patients stayed alive on study [Up to 6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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