Based on promising laboratory data, the MecMeth study brings combined temozolomide (TMZ)/meclofenamate (MFA) therapy into clinical use for the first time in patients with relapsed, MGMT promoter-methylated glioblastoma. Meclofenamate disrupts therapy resistance-mediated tumor cell networks, making tumor cells more sensitive to chemotherapy. Phase I will determine the optimal dose of meclofenamate in combination with temozolomide, which will then be evaluated in a randomized phase II trial for early evidence of improved efficacy. Phase I will enroll a maximum of 12 patients; Phase II will consist of 2 parallel groups of 30 patients each.