Phase III Trial of Temozolomide/Lomustine (TMZ/LOM) Combination Therapy vs. Standard TMZ Therapy for Newly Diagnosed MGMT Promoter Methylated Glioblastoma (IDHwt) Patients +/- Tumor Treating Fields (Optune)

2023-506998-35-00

Background: Glioblastoma (GBM) is notoriously difficult to treat, with current therapies often extending life by only a few months. The standard treatment involves surgery followed by radiation and chemotherapy with Temozolomide (TMZ). The efficacy of TMZ, however, is significantly enhanced when the tumor's o6-methylguanine-DNA-methyltransferase (MGMT) gene is methylated. Recent studies, such as the NOA-09 trial, have suggested that adding Lomustine (LOM) to TMZ could improve outcomes for patients with this specific tumor profile. Hypothesis: The investigators hypothesize that the addition of LOM to the TMZ regimen will lead to significantly improved survival rates among patients with newly diagnosed glioblastoma who have a methylated MGMT promoter compared to those receiving only TMZ. Treatment Plans: The study will randomly assign participants to two groups: * Control Group: Standard treatment with TMZ during and after radiation therapy. * Experimental Group: TMZ combined with LOM, starting on the first day of radiation therapy. Outcome Measures: The primary outcome measure will be survival. Other outcomes will include progression-free survival (time from randomization until tumor progression or death), safety profiles (adverse effects of the treatments), and quality of life measures as well as neurocognitive outcomes.

2024-05-15

2028-12-15

2031-12-15

Not yet recruiting

Early phase I

200

Inclusion Criteria: * Newly diagnosed glioblastoma/gliosarcoma, IDH wild type * Methylated MGMT promoter * World Health Organization performance status 0-2 * Age 18-70 Exclusion Criteria: * Previous malignancy within 3 y or malignancy treated non-curatively * Previous chemotherapy or radiotherapy involving the head * Off-protocol tumor-specific treatment * Serious comorbidity

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Everyone: Radiotherapy (RT) consists of 60 Gy standard RT (RT 30x2Gy)\n\nExperimental treatment arm (TMZ/LOM):\n\n6 cycles of LOM/TMZ Start day 1 of RT. Cycle length of 42 days. Duration 9 months.\n\nStandard treatment arm (TMZ):\n\nOral TMZ 75 mg/m2 daily during RT and with start day 1 of RT. This is followed by 6 cycles of TMZ with start 4 weeks after the end of RT. Cycle length 28 days. Duration 8,5 months.\n\nEveryone: TTFields start with radiotherapy/chemotherapy - but only in Sweden where TTF is part of standard of care (SOC). Ongoing until 2nd progression or max 2 years.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 200, 'type': 'ESTIMATED'}}

2024-05-17