NCT05017610

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

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Recurrent Glioblastoma
• Recurrent Gliosarcoma

Interventions

Type	Name	Description
DRUG	Liothyronine	Given PO
DRUG	Lomustine	Given PO
DRUG	Methimazole	Given PO

Timeline

• Start date: 2021-10-20
• Primary completion: 2022-10-14
• Completion: 2022-10-14
• First posted: 2021-08-24
• Last updated: 2022-12-02

Regulatory

• FDA-regulated drug study