Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Gliosarcoma

Disease Attributes

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Lomustine

Methimazole

Antineoplastic Agents, Alkylating

Alkylating Agents

Antithyroid Agents

Hormones

Hormone Antagonists

Liothyronine

Jeffrey J. Olson, MD

This early phase I trial studies the safety and feasibility of inducing a hypothyroxinemic state in patients with glioblastoma or gliosarcoma that has come back (recurrent). This trial aims to see if giving a specific thyroid hormone, such as methimazole and liothyronine, is safe and could benefit cancer treatment.

PRIMARY OBJECTIVE:

I. To evaluate the safety and feasibility of inducing a hypothyroxinemic state in patients with recurrent glioblastoma.

SECONDARY OBJECTIVES:

I. To evaluate the anti-tumor activity of inducing hypothyroxinemic state by assessing progression-free survival (PFS) and overall survival (OS).

II. To evaluate the correlation of PFS and OS with thyroid hormone levels. III. To evaluate the correlation of overall response rate (ORR) with thyroid hormone levels.

IV. To evaluate the correlation of potential side effects with T3 levels or methimazole dose.

OUTLINE:

CATEGORY 1 (normal baseline thyroid function and no levothyroxine replacement): Patients receive methimazole orally (PO) daily and lomustine daily. Treatment with lomustine repeats every 6 weeks for up to 6 cycles or 12 months. Patients may receive liothyronine PO twice daily (BID) when thyroid-stimulating hormone (TSH) is above upper normal limit. Treatment continues in the absence of disease progression or unacceptable toxicity.

CATEGORY 2 (baseline primary hypothyroidism in patients taking levothyroxine): Patients receive liothyronine PO BID to maintain lower free T4 below lower limit of normal and TSH and free T3 in the normal range. At the time of cessation of exogenous T4, patients receive lomustine every 6 weeks for up to 6 cycles or 12 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

CATEGORY 3 (secondary/tertiary hypothyroidism): Patients receive liothyronine PO BID to maintain lower free T4 below lower limit of normal and free T3 within normal range. At the time of cessation of exogenous T4, patients receive lomustine every 6 weeks for up to 6 cycles or 12 months. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 and 8 weeks.

Inducing a Hypothyroxinemic State in Patients With Recurrent Glioblastoma or Gliosarcoma

A Single Arm Pilot Study to Evaluate the Safety and Feasibility of Inducing a Hypothyroxinemic State in Patients With Recurrent Glioblastoma

Descriptive statistics (e.g., frequency and percentage) for each adverse event/severe adverse event will be tabulated by association and grade.

Will be assessed by Response Assessment in Neuro-Oncology Criteria. Will be summarized with the 2-sided 95% confidence interval using the Clopper-Pearson method.

Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with a 95% confidence interval.

National Cancer Institute (NCI)

Emory University

Principal Investigator

Gland and Hormone Related Diseases

Thyroid Diseases

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.

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.

The purpose of resection is to remove as much tumor as possible to alleviate mass effect and to obtain brain tissue for experimental analysis.

Recurrent Glioblastoma Surgical Resection

Pharmacodynamic assays are intended to investigate drug and downstream drug-induced effects.

Pharmacodynamic Assays

David Peereboom, MD

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.

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.

Methimazole in Patients With Progressive Glioblastoma

Targeting Transsulfuration Via Suppression of Thyroid Hormone Signaling in Progressive Glioblastoma: Phase 2 and Pharmacodynamic Trial of Methimazole in Patients With Progressive Glioblastoma

defined as alive and free from progressive disease

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Inducing a Hypothyroxinemic State in Patients With Recurrent Glioblastoma or Gliosarcoma	NCT05017610	Recurrent Gliob... Recurrent Glios...	Liothyronine Lomustine Methimazole	18 Years -	Emory University
Methimazole in Patients With Progressive Glioblastoma	NCT05607407	Glioblastoma Glioma	Methimazole Recurrent Gliob... Pharmacodynamic...	18 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for methimazole

Every month we try and update this database with for methimazole cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for methimazole

Every month we try and update this database with for methimazole cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for methimazole cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.