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Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03514069
Recruitment Status : Recruiting
First Posted : May 2, 2018
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE April 20, 2018
First Posted Date  ICMJE May 2, 2018
Last Update Posted Date June 20, 2019
Actual Study Start Date  ICMJE June 5, 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients [ Time Frame: Up to 6 weeks ]
  • Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients [ Time Frame: Up to 6 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03514069 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2018)
  • 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.
  • 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 ]
  • Average time patients stayed alive on study [ Time Frame: Up to 6 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ruxolitinib With Radiation and Temozolomide for Grade III Gliomas and Glioblastoma
Official Title  ICMJE Phase I Study of Ruxolitinib With Radiation and Temozolomide in Patients With Newly Diagnosed Grade III Gliomas and Glioblastoma
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioma
  • Glioblastoma
Intervention  ICMJE
  • Drug: ruxolitinib
    Starting dose ruxolitinib 10 mg twice daily
  • Radiation: radiation
    60gy for 6 weeks
  • Drug: temozolomide
    75mg/m2
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: ruxolitinib
    • Radiation: radiation
  • 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

    Interventions:
    • Drug: ruxolitinib
    • Radiation: radiation
    • Drug: temozolomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2018)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Manmeet Ahluwalia, MD 866-223-8100 CancerCenterResearch@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03514069
Other Study ID Numbers  ICMJE CASE3317
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Manmeet Ahluwalia, MD Cleveland Clinic, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP