Clinical trial NCT03514069: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioma
Glioblastoma
Keywords: ruxolitinib
radiation
temozolomide
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2018-05-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients
timeFrame: Up to 6 weeks
measure: Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Number of patient study specific adverse events as a measure of safety
timeFrame: Up to 8 weeks after beginning treatment
measure: Number of patients who have experienced progression free survival as defined by the response assessment in neuro-oncology (RANO) criteria
timeFrame: Up to 6 weeks
measure: Average time patients stayed alive on study
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
name: David Peereboom, MD
role: PRINCIPAL_INVESTIGATOR
References: