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Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

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ClinicalTrials.gov Identifier: NCT03514069
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

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 Type : Interventional
Estimated 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 : June 5, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


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




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients [ Time Frame: Up to 6 weeks ]
  2. Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients [ Time Frame: Up to 6 weeks ]

Secondary Outcome Measures :
  1. Number of patient study specific adverse events as a measure of safety [ Time Frame: 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.

  2. 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 ]
  3. Average time patients stayed alive on study [ Time Frame: Up to 6 weeks ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03514069


Contacts
Contact: Manmeet Ahluwalia, MD 866-223-8100 CancerCenterResearch@ccf.org

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Manmeet Ahluwalia, MD    866-223-8100    CancerCenterResearch@ccf.org   
Principal Investigator: Manmeet Ahluwalia, MD         
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Manmeet Ahluwalia, MD Cleveland Clinic, Case Comprehensive Cancer Center

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03514069     History of Changes
Other Study ID Numbers: CASE3317
First Posted: May 2, 2018    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Case Comprehensive Cancer Center:
ruxolitinib
radiation
temozolomide

Additional relevant MeSH terms:
Glioma
Glioblastoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents