Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy (MecMeth/ NOA-24)

Trial details

Who runs it

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Trial code

EU 2024-511264-89-00

Record updated

2026. szeptember 9.

Original description

The primary objective of Phase I is to determine toxicity of meclofenamate sodium therapy in addition to standard temozolomide and, on this base, determine the daily meclofenamate sodium dose to be recommended for Phase II. In Phase II, the primary objective is efficacy of meclofenamate sodium therapy in addition to standard therapy.Read full original descriptionShow less

The primary objective of Phase I is to determine toxicity of meclofenamate sodium therapy in addition to standard temozolomide and, on this base, determine the daily meclofenamate sodium dose to be recommended for Phase II. In Phase II, the primary objective is efficacy of meclofenamate sodium therapy in addition to standard therapy.

Inclusion: 1. First relapse after first-line therapy with radiotherapy (RT) and alkylating chemotherapy, ≥ 3 months after last chemotherapy application and >6 months after end of RT. Drug therapy and/or radiotherapy for first relapse treatment not yet started; Adequate liver function (bilirubin <1.5 x ULN; ASAT /ALAT <3 x ULN, creat-inine < 1.5 x ULN; Patient compliance that allows adequate follow up; Male and female patients with reproductive potential must use an ap-proved contraceptive method during and for 3 months after the trial (Pearl index <1%); Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test (beta-HCG) must be obtained prior to treatment start; Addition criterion for Phase II only: 14. Resection at first relapse not yet performed; according to the local treating neurosurgeon and the documented decision of local neurooncological tu-mor board, reresection of the tumor is clinically indicated and can be safe-ly deferred until day 7-10 after initiation of MFA/TMZ therapy; Tumor progression according to RANO criteria; Written informed consent; Cognitive state to understand rationale and necessity of study therapy and procedures; MGMT promotor-methylated (MGMTmeth), IDH wildtype glioblastoma (GBM) or gliosarcoma confirmed with histology of the primary resection or, in phase II, last resection; Age > 18 years; Karnofsky performance score (KPS) ≥50%; Life expectancy > 6 months; Adequate bone marrow reserve (WBC >3 G/nl, platelets >100 G/nl.

Exclusion: Indication for hematotoxicity in first-line therapy not allowing TMZ starting dose 150 mg/m2/d at the discretion of the investigator; Treatment in another clinical trial with therapeutic medical intervention or use of any other investigational agent during the trial or within the 30 days before enrollment; Medication with a drug that is not allowed in conjunction with MFA intake and cannot be discontinued: i.e. lithium, methotrexate, etc; The presence of any other concomitant severe, progressive, or uncon-trolled renal, hepatic, hematological, endocrine, pulmonary, cardiac (in-cluding coronary artery bypass graft), or psychiatric disease, or signs and symptoms thereof, that may affect the subjects participation in the study, according to investigators judgement; Unable to undergo contrast-enhanced MRI (i.e. contrast allergy, implants, etc; Medical History of gastrointestinal Resection of any kind that may poten-tially alter the absorption of the investigational study drug, according to investigators judgement; History of temozolomide-related liver toxicity > CTCAE5 grade 1 or skin toxicity > CTCAE5 grade 2 in first-line therapy; History of gastrointestinal bleeding or gastroduodenal ulcer, active gastritis; History of NSAID-related asthma, urticaria or allergic-type skin reactions; Uncontrolled malignancy within the last 2 years; History of confirmed or suspected hypersensitivity (delayed type and im-mediate type, inclusive of anaphylactic reaction) to any background/ standard TMZ drug product or one of its ingredients of the chosen prod-uct, or to cyclooxygenase inhibitors (“NSAIDs”), or to any ingredient of meclofenamate drug product; History of other disease with poor prognosis; History of severe coronary heart disease (esp. after coronary artery bypass graft or history of myocardial infarction)or severe heart failure; Known HIV infection, active hepatitis B or C; Patients with active bleeding, bleeding diathesis, antiplatelet therapy or anticoagulant therapy except for the following anticoagulants which are permitted for low-dose thrombosis prophylaxis up to the dosage speci-fied here: unfractionated heparin 7,500 IU BID or 5,000 IU TID; low molecu-lar weight heparin e. g. enoxaparin 40 mg/d; fondaparinux 2.5 mg/d; danaparoid sodium 750 IU BID; argatroban IV route thrombin time < 70 s; dabigatran 110 mg BID; rivaroxaban 10 mg/d; edoxaban 30 mg/d; epixa-ban 2.5 mg BID This restriction is due to a potentially increased risk of GI ulcers with subsequent bleeding under MFA therapy. (Not applicable for Phase II); Patients with medically diagnosed hereditary Galactose Intolerance, com-plete lactase deficiency or confirmed Glucose-Galactose-Malabsorption; Breastfeeding or pregnant.

EU CTIS 2024-511264-89-00