GlioblastomaPhase 1NCT03535350
Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
A Phase 1 study testing Ibrutinib, Radiation and Temozolomide (TMZ) in people with Glioblastoma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Ibrutinib, Radiation and Temozolomide (TMZ)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2018to 4 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: Phase I Study of Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
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.
Read the 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.
November 2020:
420 mg of ibrutinib plus temozolomide and radiation was found to be safe - up to 36 participants can be treated at the expansion cohort in both arm 1 and arm 2.
- Conditions
- Glioblastoma
- Keywords
- ibrutinib, temozolomide, brain cancer
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
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.
RadiationRadiation
2Gy x 30minutes for 6 weeks.
Temozolomide (TMZ)Drug
Also called Temodar, Methazolastone
Cycle 1 150mg/m2 and cycle 2-6 will be up to 200mg/m2.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ibrutinib; Radiation: Radiation; Drug: Temozolomide (TMZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of ibrutinib
Determination of MTD of Ibrutinib with methylated or unmethylated glioblastoma
Measured: 6 weeks
Secondary outcomes (3)
Number of patients who experience adverse events
Safety of combination of Ibrutinib with Radiation or Ibrutinib with Temozolomide and Radiation
Measured: 10 weeks
Number of patients with Progression Free Survival (PFS)
Number of patients that are alive without disease progression
Measured: 10 weeks
Length of time of overall survival
Patient survival at time of last assessment
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2018
- Study start24 Aug 2018
- Primary completion4 Apr 2023
- Study completion4 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Peereboom, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03535350
- Sponsor's protocol ID
- CASE2317
- Status last verified
- Oct 2026
- First submitted
- 14 May 2018
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Ibrutinib With Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma
- ClinicalTrials.gov ID
- NCT03535350
- Acronym / sponsor ID
- CASE2317
- Conditions
- Glioblastoma
- Keywords
- ibrutinib, temozolomide, brain cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 24 Aug 2018 (actual)
- Primary completion
- 4 Apr 2023 (actual)
- Study completion
- 4 Apr 2023 (actual)
- First posted
- 24 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
November 2020:
420 mg of ibrutinib plus temozolomide and radiation was found to be safe - up to 36 participants can be treated at the expansion cohort in both arm 1 and arm 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Unmethylated MGMT Glioblastoma | Experimental | Drug: Ibrutinib, Radiation: RadiationEvery 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. |
| Methylated MGMT Glioblastoma | Experimental | Drug: Ibrutinib, Radiation: Radiation, Drug: Temozolomide (TMZ)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: ImbruvicaDose 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. | Drug | Methylated MGMT Glioblastoma, Unmethylated MGMT Glioblastoma |
| Radiation2Gy x 30minutes for 6 weeks. | Radiation | Methylated MGMT Glioblastoma, Unmethylated MGMT Glioblastoma |
| Temozolomide (TMZ)Also: Temodar, MethazolastoneCycle 1 150mg/m2 and cycle 2-6 will be up to 200mg/m2. | Drug | Methylated MGMT Glioblastoma |
Primary outcome
Maximum tolerated dose (MTD) of ibrutinib
Time frame: 6 weeks
Determination of MTD of Ibrutinib with methylated or unmethylated glioblastoma
3 secondary outcomes
Number of patients who experience adverse events
Time frame: 10 weeks
Number of patients with Progression Free Survival (PFS)
Time frame: 10 weeks
Length of time of overall survival
Time frame: 10 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Peereboom, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ibrutinib, Radiation and Temozolomide (TMZ) in people with Glioblastoma, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of ibrutinib (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.