NCT05095376

Testing the Addition of the Chemotherapy Drug Lomustine (Gleostine) to the Usual Treatment (Temozolomide and Radiation Therapy) for Newly Diagnosed MGMT Methylated Glioblastoma

A Phase III Trial of Lomustine-Temozolomide Combination Therapy Versus Standard Temozolomide in Patients With Methylated MGMT Promoter Glioblastoma

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 265 (actual)
• Sponsor: NRG Oncology · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of adding lomustine to standard chemotherapy with temozolomide and radiation therapy versus temozolomide and radiation therapy alone in shrinking or stabilizing newly diagnosed MGMT methylated glioblastoma. MGMT methylated tumors are more likely to respond to temozolomide chemotherapy. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's DNA and may kill tumor cells. Radiation therapy uses high energy x-ray photons to kill tumor cells and shrink tumors. Adding lomustine to standard chemotherapy with temozolomide and radiation therapy may shrink or stabilize glioblastoma.

Detailed description

PRIMARY OBJECTIVE: I. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) significantly prolongs overall survival (OS) versus (vs.) standard chemoradiotherapy with temozolomide in patients with newly diagnosed glioblastoma (GBM) with MGMT promoter methylation. SECONDARY OBJECTIVES: I. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) significantly prolongs progression-free survival (PFS) vs. standard chemoradiotherapy with temozolomide in patients with newly diagnosed GBM with MGMT promoter methylation. II. To compare the two different chemotherapy regimens on patient-reported outcomes (PROs), as measured by the MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) in patients with newly diagnosed GBM with MGMT promoter methylation. III. To determine if the regimen with the two alkylating agents temozolomide and lomustine with radiotherapy (RT) is associated with inferior short-term change in PROs as measured by MDASI-BT vs. standard chemoradiotherapy with temozolomide in patients with newly diagnosed GBM with MGMT promoter methylation. IV. To assess toxicity in the two different chemotherapy regimens. EXPLORATORY OBJECTIVES: I. To assess the association between absolute lymphocyte counts and outcomes. II. To assess the association between CD4+ lymphocyte counts and outcomes. III. To compare the two different chemotherapy regimens in terms of long-term PROs as measured by MDASI-BT at years 1 and 2. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo radiation therapy 5 days per week and receive temozolomide orally (PO) once daily (QD) for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive temozolomide PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) throughout the trial. ARM II: Patients undergo radiation therapy 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive lomustine PO on day 1 of each cycle and temozolomide PO QD on days 2-6 of each cycle. Treatment repeats every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial. After completion of study treatment, patients are followed up every 3 months for year 1, every 4 months for year 2, and then every 6 months thereafter.

Conditions

• Glioblastoma
• Gliosarcoma

Interventions

Type	Name	Description
DRUG	Lomustine	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
RADIATION	Photon Beam Radiation Therapy	Undergo radiation therapy
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Temozolomide	Given PO

Timeline

• Start date: 2022-03-28
• Primary completion: 2026-08-08
• Completion: 2026-08-08
• First posted: 2021-10-27
• Last updated: 2026-04-03

Locations

420 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study