Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma

NCT03535350 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE2317
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma

Keywords

ibrutinib; temozolomide; brain cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of ibrutinib

  Determination of MTD of Ibrutinib with methylated or unmethylated glioblastoma

  6 weeks

Secondary Outcomes (3)

• Number of patients who experience adverse events

  10 weeks

• Number of patients with Progression Free Survival (PFS)

  10 weeks

• Length of time of overall survival

  10 weeks

Study Arms (2)

Unmethylated MGMT Glioblastoma

EXPERIMENTAL

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.

Drug: Ibrutinib; Radiation: Radiation

Methylated MGMT Glioblastoma

EXPERIMENTAL

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.

Drug: Ibrutinib; Radiation: Radiation; Drug: Temozolomide (TMZ)

Interventions

Ibrutinib DRUG

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. November 2020: 420 mg of ibrutinib plus temozolomide and radiation was found to be safe - up to 36 participants can betreated at the expansion cohort in both arm 1 and arm 2.

Also known as: Imbruvica

Methylated MGMT Glioblastoma; Unmethylated MGMT Glioblastoma

Radiation RADIATION

2Gy x 30minutes for 6 weeks.

Methylated MGMT Glioblastoma; Unmethylated MGMT Glioblastoma

Temozolomide (TMZ) DRUG

Cycle 1 150mg/m2 and cycle 2-6 will be up to 200mg/m2.

Also known as: Temodar, Methazolastone

Methylated MGMT Glioblastoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

ibrutinib; Radiation; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• David Peereboom, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: May 14, 2018
• First Posted: May 24, 2018
• Study Start: August 24, 2018
• Primary Completion: April 4, 2023
• Study Completion: December 30, 2025
• Last Updated: September 30, 2025

Record last verified: 2025-01

Locations

US (1)