GlioblastomaPhase 2NCT05607407
Methimazole in Patients With Progressive Glioblastoma
A Phase 2 study testing Methimazole, Recurrent Glioblastoma Surgical Resection and Pharmacodynamic Assays in people with Glioblastoma and Glioma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioma
- What is being tested?
- Methimazole, Recurrent Glioblastoma Surgical Resection and Pharmacodynamic Assays
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Jan 2023to Sep 2026
- Phase
- Phase 2
- 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
- Subjects must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for which a clinically indicated tumor resection is planned.
- Subjects must not have received methimazole for this disease.
- Age is greater than or equal to 18 years of age
- Performance status: Karnofsky Performance status ≥ 70%
- Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below: Hemoglobin ≥ 8 g/dl, Absolute neutrophil count ≥ 1,200/mcL, Platelet count ≥ 75,000/mcL, Total bilirubin < 1.5 x institutional upper limit of normal (ULN), AST (SGOT) ≤ 3 X institutional ULN, ALT (SGPT) ≤ 3 X institutional ULN, Calculated creatinine clearance > 50 mL/min, Prothrombin time/international normalized ratio (PT/INR) <1.4 for patients not on warfarin, Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices), In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
- Subjects must have normal thyroid function within 21 days of study entry as defined below: ≤ 3 X institutional ULN
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- Women of childbearing potential must have a negative pregnancy test within 21 days of study entry. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Men of reproductive potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and through 30 days after the last dose of study drug.
- Patients must be able to swallow whole tablets.
- Patients must have the following minimum intervals from prior treatments: surgery - 4 weeks, nitrosoureas - 6 weeks, cytotoxic chemotherapy - standard intervals depending on the most recent regimen. i.e., for temozolomide 5 of 28, 23 days after most recent temozolomide; for temozolomide 21 of 28 days, 7 days after most recent dose; etoposide 14 of 21 days, 7 days after last dose. For drugs not listed, the research nurse, treating investigator, and principal investigator will determine the appropriate interval, Investigational therapy or non-cytotoxic therapy - 2 weeks, For bevacizumab - 4 weeks from anticipated date of protocol surgery
- Patients positive for human immunodeficiency virus (HIV) are allowed on study (note: HIV testing is not required), but HIV-positive patients must have: An undetectable viral load within 6 months of registration, A stable regimen of highly active anti-retroviral therapy (HAART), No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- For patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patient must be deemed by investigator to be a candidate for post-operative chemotherapy.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy.
- Subjects receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to methimazole.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, patients with prior or concurrent malignancy are eligible.
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] diarrhea of any etiology at screening).
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- Pregnant or breastfeeding.
- Known history of hyperthyroidism or hypothyroidism
- Unable or unwilling to swallow tablets.
- Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
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: Targeting Transsulfuration Via Suppression of Thyroid Hormone Signaling in Progressive Glioblastoma: Phase 2 and Pharmacodynamic Trial of Methimazole in Patients With Progressive Glioblastoma
The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Different doses of Methimazole will be given to several study participants with glioblastoma. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the side effects occur that require the dose to be lowered. The procedures in this study are research blood draws, physical exams, collection of medical history, MRI scans, and study drug administration.
Read the detailed description
Hydrogen sulfide (H2S), a by-product of cysteine metabolism, inhibits the growth of cultured glioblastoma cells and impairs progression of glioblastoma tumors developing in vivo in laboratory mice. Additionally, endogenous H2S production and signaling via protein sulfhydration are decreased in human glioblastoma brain tissues compared to non-cancerous brain tissue. Thus, boosting H2S levels is a promising and novel therapeutic strategy for treating glioblastoma. The use of exogenous H2S is difficult to translate to the clinic due to toxicity and volatility. Therefore, bolstering endogenous H2S synthesis and signaling represents a safe and promising method to mitigate disease progression. Based on previously published data, which detailed the use of the thyroid hormone inhibitor propylthiouracil (PTU) to enhance endogenous H2S production in mice, and a previous clinical trial at CCF utilizing PTU to increase the survival of glioblastoma patients, revisiting the use of thyroid hormone inhibitors to de-repress endogenous H2S production concurrent with standards of care poses a novel therapeutic avenue. In the nearly two decades since the aforementioned clinical trial, PTU has been largely replaced in clinical endocrinology by the safer and more efficient thyroid inhibitor methimazole. Given our recent success elucidating the importance of tumor suppressive H2S in the realm of GBM, it is hypothesized that reduced thyroid hormone production via oral methimazole intake will bolster the effectiveness of frontline therapy and extend survival by boosting H2S production and function within the tumor-bearing brain. The goal of this trial is to provide proof of the concept that suppression of thyroid hormone signaling via methimazole and subsequent augmentation of H2S synthesis and signaling is feasible in patients with glioblastoma. Achievement of this goal will motivate and guide further therapeutic development of this combinatorial therapeutic approach.
- Conditions
- Glioblastoma, Glioma
- Being tested
- Methimazole, Recurrent Glioblastoma Surgical Resection, Pharmacodynamic Assays
- Keywords
- Transsulfuration, Methimazole
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethimazoleDrug
Also called Northyx, Tapazole
Starting dose: Methimazole 15 mg/d. Six participants will receive this dose. If they achieve a 10% increase in peripheral blood H2S concentrations, an additional 13 participants will receive this dose to accrue a total of 19 participants for which a preliminary estimate of PFS6 can be calculated. If the first 6 participants do not achieve a 10% increase in peripheral blood H2S concentrations, the dose will be increased to the second and final dose level of 25 mg/d at which 19 participants will be treated.
Recurrent Glioblastoma Surgical ResectionProcedure or surgery
The purpose of resection is to remove as much tumor as possible to alleviate mass effect and to obtain brain tissue for experimental analysis.
Pharmacodynamic AssaysDiagnostic test
Pharmacodynamic assays are intended to investigate drug and downstream drug-induced effects.
| Study group | Role | What they receive |
|---|---|---|
| Surgical Resection, Pharmacodynamic Assays, and Methimazole | Experimental | Participants with recurrent glioblastoma for whom surgical resection is indicated will have baseline peripheral blood pharmacodynamic assays (PBPD) followed by oral mehimazole at least 5 days pre-operatively or until lower circulating theyroid hormone levels are achieved. PBPD assays will then be repeated. After surgical resection, PBPD will be repeated a day later. When the participant is deemed able to begin methimazole (no sooner than 10 days post-op) PBPD assays will be repeated and the participant will begin methimazole for 4 weeks. At the end of the first 4 week cycle, an MRI will be performed. PBPD assays will be repeated after which secondary chemotherapy will be added at the treating physician's discretion. After 4 weeks, PBPD will be repeated and the participant will undergo another MRI at 8 weeks. Receives: Drug: Methimazole; Procedure: Recurrent Glioblastoma Surgical Resection; Diagnostic Test: Pharmacodynamic Assays |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) Rate
defined as alive and free from progressive disease
Measured: Up to 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2022
- Study start30 Jan 2023
- Primary completionSep 2026 (estimated)
- Study completionSep 2026 (estimated)
Why it stopped: On hold per study team
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (estimated)
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
- NCT05607407
- Sponsor's protocol ID
- CASE3322
- Status last verified
- Aug 2026
- First submitted
- 26 Oct 2022
- Last updated
- 17 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Transsulfuration Via Suppression of Thyroid Hormone Signaling in Progressive Glioblastoma: Phase 2 and Pharmacodynamic Trial of Methimazole in Patients With Progressive Glioblastoma
- ClinicalTrials.gov ID
- NCT05607407
- Acronym / sponsor ID
- CASE3322
- Conditions
- Glioblastoma, Glioma
- Keywords
- Transsulfuration, Methimazole
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: On hold per study team
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 30 Jan 2023 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 7 Nov 2022 (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.
The purpose of this study is to test the effectiveness, safety, and tolerability of a drug called Methimazole. The investigational drug, Methimazole is not FDA approved for brain tumors, but it is used to treat thyroid illnesses. Different doses of Methimazole will be given to several study participants with glioblastoma. The first several study participants will receive the lowest dose. If the drug does not cause serious side effects, it will be given to other study participants at a higher dose. The doses will continue to increase for every group of study participants until the side effects occur that require the dose to be lowered. The procedures in this study are research blood draws, physical exams, collection of medical history, MRI scans, and study drug administration.
Detailed description
Hydrogen sulfide (H2S), a by-product of cysteine metabolism, inhibits the growth of cultured glioblastoma cells and impairs progression of glioblastoma tumors developing in vivo in laboratory mice. Additionally, endogenous H2S production and signaling via protein sulfhydration are decreased in human glioblastoma brain tissues compared to non-cancerous brain tissue. Thus, boosting H2S levels is a promising and novel therapeutic strategy for treating glioblastoma. The use of exogenous H2S is difficult to translate to the clinic due to toxicity and volatility. Therefore, bolstering endogenous H2S synthesis and signaling represents a safe and promising method to mitigate disease progression. Based on previously published data, which detailed the use of the thyroid hormone inhibitor propylthiouracil (PTU) to enhance endogenous H2S production in mice, and a previous clinical trial at CCF utilizing PTU to increase the survival of glioblastoma patients, revisiting the use of thyroid hormone inhibitors to de-repress endogenous H2S production concurrent with standards of care poses a novel therapeutic avenue. In the nearly two decades since the aforementioned clinical trial, PTU has been largely replaced in clinical endocrinology by the safer and more efficient thyroid inhibitor methimazole. Given our recent success elucidating the importance of tumor suppressive H2S in the realm of GBM, it is hypothesized that reduced thyroid hormone production via oral methimazole intake will bolster the effectiveness of frontline therapy and extend survival by boosting H2S production and function within the tumor-bearing brain. The goal of this trial is to provide proof of the concept that suppression of thyroid hormone signaling via methimazole and subsequent augmentation of H2S synthesis and signaling is feasible in patients with glioblastoma. Achievement of this goal will motivate and guide further therapeutic development of this combinatorial therapeutic approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Surgical Resection, Pharmacodynamic Assays, and Methimazole | Experimental | Drug: Methimazole, Procedure: Recurrent Glioblastoma Surgical Resection, Diagnostic Test: Pharmacodynamic AssaysParticipants with recurrent glioblastoma for whom surgical resection is indicated will have baseline peripheral blood pharmacodynamic assays (PBPD) followed by oral mehimazole at least 5 days pre-operatively or until lower circulating theyroid hormone levels are achieved. PBPD assays will then be repeated. After surgical resection, PBPD will be repeated a day later. When the participant is deemed able to begin methimazole (no sooner than 10 days post-op) PBPD assays will be repeated and the participant will begin methimazole for 4 weeks. At the end of the first 4 week cycle, an MRI will be performed. PBPD assays will be repeated after which secondary chemotherapy will be added at the treating physician's discretion. After 4 weeks, PBPD will be repeated and the participant will undergo another MRI at 8 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subjects must have histologically or cytologically confirmed WHO grade 4 glioma (including tumors with molecularly defined grade 4 astrocytoma) for which a clinically indicated tumor resection is planned.
- Subjects must not have received methimazole for this disease.
- Age is greater than or equal to 18 years of age
- Performance status: Karnofsky Performance status ≥ 70%
- Subjects must have adequate organ function and laboratory parameters within 21 days of study entry as defined below: Hemoglobin ≥ 8 g/dl, Absolute neutrophil count ≥ 1,200/mcL, Platelet count ≥ 75,000/mcL, Total bilirubin < 1.5 x institutional upper limit of normal (ULN), AST (SGOT) ≤ 3 X institutional ULN, ALT (SGPT) ≤ 3 X institutional ULN, Calculated creatinine clearance > 50 mL/min, Prothrombin time/international normalized ratio (PT/INR) <1.4 for patients not on warfarin, Patients on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices), In-range INR (between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
Key exclusion criteria (10 listed)
- Prior treatment toxicities not resolved to ≤ Grade 1 according to NCI CTCAE Version 5.0 except alopecia and neuropathy.
- Subjects receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to methimazole.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Other prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are excluded. Otherwise, patients with prior or concurrent malignancy are eligible.
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 |
|---|---|---|
| MethimazoleAlso: Northyx, TapazoleStarting dose: Methimazole 15 mg/d. Six participants will receive this dose. If they achieve a 10% increase in peripheral blood H2S concentrations, an additional 13 participants will receive this dose to accrue a total of 19 participants for which a preliminary estimate of PFS6 can be calculated. If the first 6 participants do not achieve a 10% increase in peripheral blood H2S concentrations, the dose will be increased to the second and final dose level of 25 mg/d at which 19 participants will be treated. | Drug | Surgical Resection, Pharmacodynamic Assays, and Methimazole |
| Recurrent Glioblastoma Surgical ResectionThe purpose of resection is to remove as much tumor as possible to alleviate mass effect and to obtain brain tissue for experimental analysis. | Procedure or surgery | Surgical Resection, Pharmacodynamic Assays, and Methimazole |
| Pharmacodynamic AssaysPharmacodynamic assays are intended to investigate drug and downstream drug-induced effects. | Diagnostic test | Surgical Resection, Pharmacodynamic Assays, and Methimazole |
Primary outcome
Progression Free Survival (PFS) Rate
Time frame: Up to 6 months after treatment
defined as alive and free from progressive disease
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 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 2 study testing Methimazole, Recurrent Glioblastoma Surgical Resection and Pharmacodynamic Assays in people with Glioblastoma and Glioma, 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 14 inclusion and 10 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: paused, as of the sponsor's last update on 17 Aug 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Progression Free Survival (PFS) Rate (time frame: Up to 6 months after treatment). 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 17 Aug 2026.