Clinical Trials /

Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma

NCT03535350

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
  • Official Title: Phase I Study of Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Clinical Trial IDs

  • ORG STUDY ID: CASE2317
  • NCT ID: NCT03535350

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
IbrutinibImbruvicaUnmethylated MGMT Glioblastoma
Temozolomide (TMZ)Temodar, MethazolastoneMethylated MGMT Glioblastoma

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Unmethylated MGMT GlioblastomaExperimentalEvery 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.
  • Ibrutinib
Methylated MGMT GlioblastomaExperimentalEvery 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.
  • Ibrutinib
  • Temozolomide (TMZ)

Eligibility Criteria

        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
      
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 ibrutinib
Time Frame:6 weeks
Safety Issue:
Description:Determination of MTD of Ibrutinib with methylated or unmethylated glioblastoma

Secondary Outcome Measures

Measure:Number of patients who experience adverse events
Time Frame:10 weeks
Safety Issue:
Description:Safety of combination of Ibrutinib with Radiation or Ibrutinib with Temozolomide and Radiation
Measure:Number of patients with Progression Free Survival (PFS)
Time Frame:10 weeks
Safety Issue:
Description:Number of patients that are alive without disease progression
Measure:Length of time of overall survival
Time Frame:10 weeks
Safety Issue:
Description:Patient survival at time of last assessment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • ibrutinib
  • temozolomide
  • brain cancer

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