Inducing a Hypothyroxinemic State in Patients With Recurrent Glioblastoma or Gliosarcoma

NCT05017610 | Withdrawn Early Phase 1 DMC FDA Drug

• 4 other identifiers: STUDY00002497NCI-2021-02249WINSHIP5264-21P30CA138292
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Recurrent Glioblastoma; Recurrent Gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

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

  Up to study completion, an average of 2 years

Secondary Outcomes (3)

• Overall response rate

  Up to study completion, an average of 2 years

• Progression free survival

  Up to study completion, an average of 2 years

• Overall survival

  Up to study completion, an average of 2 years

Study Arms (1)

Treatment (methimazole, lomustine, liothyronine)

EXPERIMENTAL

See Outline in Detailed Description.

Drug: Liothyronine; Drug: Lomustine; Drug: Methimazole

Interventions

Liothyronine DRUG

Given PO

Also known as: L-Triiodothyronine, Therapeutic T3, Triiodothyronine

Treatment (methimazole, lomustine, liothyronine)

Lomustine DRUG

Given PO

Also known as: 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, 1-Nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-, Belustin, Belustine, CCNU, Cecenu, CeeNU, Chloroethylcyclohexylnitrosourea, Citostal, Gleostine, Lomeblastin, Lomustinum, Lucostin, Lucostine, N-(2-Chloroethyl)-N''-cyclohexyl-N-nitrosourea, Prava, RB-1509, WR-139017

Treatment (methimazole, lomustine, liothyronine)

Methimazole DRUG

Given PO

Also known as: Tapazole

Treatment (methimazole, lomustine, liothyronine)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 70%) within a 14-day window prior to randomization
• Patients must have histologically confirmed glioblastoma (or gliosarcoma) at first or second recurrence after initial standard, control or experimental, therapy that includes at least radiation therapy (RT) and temozolomide (TMZ)
• Evidence of progressive disease (PD) by modified response assessment in neuro-oncology criteria (using the post-chemoradiation time point as baseline), defined by any of the following:
• \>= 25% increase in sum of products of perpendicular diameters of measurable enhancing lesions, compared with the smallest tumor measurement obtained either at the post-chemoradiation baseline (if no decrease) or best response (on stable or increasing steroid dose).
• Any new measurable (\> 1 x 1 cm) enhancing lesions after the post-chemoradiation scan
• A total of at least 2 serial magnetic resonance imaging (MRI) scans documented at Screening including: 1) a scan at the time of suspected tumor progression; and 2) a scan prior to the time of progression. Patients must have progressed after standard of care treatment (it typically includes surgery, radiation and temozolomide). Pseudoprogression or radiation necrosis has been ruled out
• Hemoglobin \>= 9.0 g/dl (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria) (within 14 days of starting treatment)
• Absolute neutrophil count (ANC) \>= 1,500/mcL (after at least 7 days without growth factor support or transfusion) (within 14 days of starting treatment)
• Platelets \>= 100,000/mcL (no transfusions allowed within 7 days of cycle 1 day 1 to meet entry criteria) (within 14 days of starting treatment)
• International normalized ratio (INR) =\< 1.5 (within 14 days of starting treatment)
• Partial thromboplastin time (PTT) \< 1.5 x upper limits of normal (ULN) (within 14 days of starting treatment)
• Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) (within 14 days of starting treatment)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.0 times the ULN (within 14 days of starting treatment)
• High amylase or lipase above upper normal limit (UNL) (within 14 days of starting treatment)

You may not qualify if:

• Patients who received temozolomide within 28 days prior to starting first cycle under this study
• Optune device is not allowed
• Patients who received prior lomustine, carmustine wafers, bevacizumab or any other anti-angiogenic agent
• Dexamethasone at time of study entry is not allowed. After a stable dose of methimazole and T3 is reached, dexamethasone can be used with a dose determined by treating physician
• 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
• Computed tomography (CT) scan with contrast within 6 weeks from enrollment as it may influence thyroid tests due to the iodine content
• History of cardiac arrhythmias (in particular, sinus bradycardia, atrial fibrillation or flutter, atrioventricular \[AV\] block, prolonged QTc, ventricular arrythmias, pacemaker, or implantable cardiac defibrillator).). Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 6 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; left ventricular ejection fraction less than or equal to 35%;New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade \>= 3 hypertension (diastolic blood pressure \>= 100 mmHg or systolic blood pressure \>= 160 mmHg) despite antihypertensive therapy, or use of amiodarone within the last 6 months.
• Uncontrolled type 2 diabetes mellitus (T2DM) (HbA1C greater than 8%) or a history of frequent hypoglycemia, or significantly uncontrolled hyperglycemia
• Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects of the study drugs. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs breastfeeding should be discontinued if the mother will be on treatment
• Early disease progression prior to 3 months (12 weeks) from the completion of RT-TMZ, unless histologically proven to be recurrent GBM
• Had more than 2 prior lines for chemotherapy administration. NOTE: In the 1st line adjuvant setting, combination of TMZ with an experimental agent, is considered one line of chemotherapy
• Any prior treatment with an intracerebral agent
• Receiving additional, concurrent, active therapy for GBM outside of the trial
• Extensive leptomeningeal disease and defined by the principal investigator (PI)
• History of allergy or hypersensitivity to any of the study treatments or any of their excipient

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Triiodothyronine; Lomustine; Methimazole

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

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Sulfhydryl Compounds; Sulfur Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey J. Olson, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 24, 2021
• Study Start: October 20, 2021
• Primary Completion: October 14, 2022
• Study Completion: October 14, 2022
• Last Updated: December 2, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share