Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed 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: NCT03535350
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : January 3, 2020
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE May 14, 2018
First Posted Date  ICMJE May 24, 2018
Last Update Posted Date January 3, 2020
Actual Study Start Date  ICMJE August 20, 2018
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
Maximum tolerated dose (MTD) of ibrutinib [ Time Frame: 6 weeks ]
Determination of MTD of Ibrutinib with methylated or unmethylated glioblastoma
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03535350 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
  • Number of patients who experience adverse events [ Time Frame: 10 weeks ]
    Safety of combination of Ibrutinib with Radiation or Ibrutinib with Temozolomide and Radiation
  • Number of patients with Progression Free Survival (PFS) [ Time Frame: 10 weeks ]
    Number of patients that are alive without disease progression
  • Length of time of overall survival [ Time Frame: 10 weeks ]
    Patient survival at time of last assessment
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 Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Official Title  ICMJE Phase I Study of Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
Brief Summary Safety of combination of ibrutinib and radiation at various dose levels in unmethylated o6-methylguanine-DNA-methyltransferase (MGMT) glioblastoma and study of ibrutinib, temozolomide, and radiation combination therapy in methylated MGMT glioblastoma.
Detailed Description There are a number of brain tumor studies including those in NCI consortium that are not including temozolomide for increased toxicity with novel agents or other drugs when added to temozolomide and radiation. However,if the combination of ibrutinib and radiation in unmethylated MGMT glioblastoma patient population is safe at every dose level we can study the safety of ibrutinib, radiation and Temozolomide in the methylated patient population. Concomitant use of radiation will lead to break down of the blood brain barrier and increase ibrutinib delivery to the brain tumor and hence the rationale to combine ibrutinib with radiation with or without temozolomide.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A standard phase 1 design will be used with 3 patients treated at each dose level and monitored for treatment-related toxicities. Escalation to the next dose will proceed in the absence of dose-limiting toxicities (DLTs).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE
  • Drug: Ibrutinib
    Dose response of Ibrutinib. Level 1 starting dose is 420mg daily. Level 2 starting dose is 560mg daily. Level -1 starting dose is 280mg daily.
    Other Name: Imbruvica
  • Radiation: Radiation
    2Gy x 30minutes for 6 weeks.
  • Drug: Temozolomide (TMZ)
    Cycle 1 150mg/m2 and cycle 2-6 will be up to 200mg/m2.
    Other Names:
    • Temodar
    • Methazolastone
Study Arms  ICMJE
  • Experimental: Unmethylated MGMT Glioblastoma
    Every patient gets ibrutinib + radiation over 6 weeks. Patients will undergo a 4-week break and then Ibrutinib treatment will continue until disease progression, intolerable toxicity, or death.
    Interventions:
    • Drug: Ibrutinib
    • Radiation: Radiation
  • Experimental: Methylated MGMT Glioblastoma
    Every patient gets ibrutinib + radiation + daily Temozolomide (TMZ) (75mg/m2) for 6 weeks. Patients will undergo a 4-week break and patients will then receive daily ibrutinib and adjuvant Temozolomide for Days 1-5 of a 28-day cycle of temozolomide for 6 cycles. The temozolomide will continue until disease progression, intolerable toxicity, or death or maximum of 6 cycles. Ibrutinib treatment will continue until disease progression, intolerable toxicity, or death.
    Interventions:
    • Drug: Ibrutinib
    • Radiation: Radiation
    • Drug: Temozolomide (TMZ)
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: May 14, 2018)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date June 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Arm 1:

  • Supratentorial unmethylated MGMT glioblastoma
  • Gadolinium MRI or contrast CT within 28 days of starting treatment
  • Karnofsky performance ≥ 70% (http://www.npcrc.org/files/news/karnofsky_performance_scale.pdf)
  • Absolute neutrophil count > 1500/mm3, platelets > 100,000/mm3, Creatinine ≤ 1.7 mg/dl, total bilirubin ≤ 1.5mg/dl, transaminases ≤ 3 times above the upper limits of normal
  • Must be able to provide written informed consent
  • Patients of reproductive potential must use an acceptable form of birth control to avoid contraception during the period of therapy and up to 90 days after the last dose of study drug. (eg. implants, injectable, oral contraceptives, intrauterine device (IUD), abstinence, and a barrier method which includes, but is not limited to condoms, vaginal rings, and sponges)
  • Female patients must have a negative pregnancy test upon study entry.
  • No concurrent malignancy with the exception of curatively treated early stage bladder and prostate cancer, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Any other prior malignancies must be disease free for ≥ 3 years.
  • Prothrombin time (PT) / international normalized ratio (INR) < 1.5 x upper limit of normal (ULN) and partial thromboplastin time (PTT) (aPTT) < 1.5 x ULN
  • Patient with any surgery more than stereotactic biopsy are eligible so that there is enough tissue for MGMT analysis.

Arm 2:

  • Arm 1 inclusion criteria must be met with the exception of the histology of the cancer, which must be methylated MGMT glioblastoma

Exclusion Criteria:

  • Serious concurrent infection or illness
  • Patients who are pregnant or breastfeeding
  • Patients receiving concurrent therapy for their tumor
  • Concurrent or prior malignancy unless curatively treated carcinoma-in-situ or basal cell carcinoma of the skin.
  • Repeat craniotomy for tumor therapy after receiving radiation and TMZ treatment.
  • Patients who received other chemotherapy or investigational agents in addition to radiation therapy and accompanying TMZ treatment.
  • Previous ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor use or allergies to components of the study drug.
  • Use of anticoagulants (including warfarin, other coumadin-derivative anticoagulant, vitamin K antagonists, or low molecular weight heparin)
  • Use of drugs known to be moderate and strong inhibitor or inducers of the P450 isoenzyme CYP3A. Participants must be off P450/CYP3A inhibitors and inducers for at least a week prior to starting the study drug.
  • Active, significant liver impairment (Child-Pugh class B or C)
  • Patient is using systemic immunosuppressant therapy, including cyclosporineA, tacrolimus, sirolimus, and other such medications, or chronic administration of > 5 mg/day or prednisone or the equivalent.Participants must be off of immunosuppressant therapy for at least 21days prior to the first dose of the study drug. Patients can be on steroids for brain edema.
  • Significant EKG abnormalities and active and significant cardiovascular disease within 6 months of screening.
  • Pregnant or breastfeeding women. Male patients that intend to father a child while enrolled or 90 days after the last dose of the study drug.
  • Unwillingness to comply with the protocol
  • Uncontrolled, active systemic infection.
  • Major surgery within 4 weeks of first dose of study drug.
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug.
  • Known bleeding disorders
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 NCT03535350
Other Study ID Numbers  ICMJE CASE2317
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: 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 Taussig Cancer Institute, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date January 2020

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