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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| ruxolitinib | | ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m |
| temozolomide | | ruxolitinib + 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
| Name | Type | Description | Interventions |
|---|
| ruxolitinib + radiation x 60 Gy for 6 weeks | Experimental | 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 | |
| ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m | Experimental | 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 | |
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
Last Updated
June 4, 2021
