Meclofenamate sodium for Glioblastoma

Inclusion criteria

• {"criterion_text":"- 1. 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."}
• {"criterion_text":"- 10. Adequate liver function (bilirubin <1.5 x ULN; ASAT /ALAT <3 x ULN, creat-inine < 1.5 x ULN"}
• {"criterion_text":"- 11. Patient compliance that allows adequate follow up"}
• {"criterion_text":"- 12. 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%)"}
• {"criterion_text":"- 13. Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test (beta-HCG) must be obtained prior to treatment start"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 2. Tumor progression according to RANO criteria"}
• {"criterion_text":"- 3. Written informed consent"}
• {"criterion_text":"- 4. Cognitive state to understand rationale and necessity of study therapy and procedures"}
• {"criterion_text":"- 5. MGMT promotor-methylated (MGMTmeth), IDH wildtype glioblastoma (GBM) or gliosarcoma confirmed with histology of the primary resection or, in phase II, last resection"}
• {"criterion_text":"- 6. Age > 18 years"}
• {"criterion_text":"- 7. Karnofsky performance score (KPS) ≥50%;"}
• {"criterion_text":"- 8. Life expectancy > 6 months"}
• {"criterion_text":"- 9. Adequate bone marrow reserve (WBC >3 G/nl, platelets >100 G/nl"}

Exclusion criteria

• {"criterion_text":"- 1. Indication for hematotoxicity in first-line therapy not allowing TMZ starting dose 150 mg/m2/d at the discretion of the investigator"}
• {"criterion_text":"- 10. Breastfeeding or pregnant"}
• {"criterion_text":"- 11. Unable to undergo contrast-enhanced MRI (i.e. contrast allergy, implants, etc"}
• {"criterion_text":"- 12. 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"}
• {"criterion_text":"- 13. Medication with a drug that is not allowed in conjunction with MFA intake and cannot be discontinued: i.e. lithium, methotrexate, etc"}
• {"criterion_text":"- 14. 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)"}
• {"criterion_text":"- 15. Patients with medically diagnosed hereditary Galactose Intolerance, com-plete lactase deficiency or confirmed Glucose-Galactose-Malabsorption"}
• {"criterion_text":"- 16. Medical History of gastrointestinal Resection of any kind that may poten-tially alter the absorption of the investigational study drug, according to investigators judgement"}
• {"criterion_text":"- 17. 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"}
• {"criterion_text":"- 2. History of temozolomide-related liver toxicity > CTCAE5 grade 1 or skin toxicity > CTCAE5 grade 2 in first-line therapy"}
• {"criterion_text":"- 3. History of gastrointestinal bleeding or gastroduodenal ulcer, active gastritis"}
• {"criterion_text":"- 4. History of NSAID-related asthma, urticaria or allergic-type skin reactions"}
• {"criterion_text":"- 5. Uncontrolled malignancy within the last 2 years"}
• {"criterion_text":"- 6. 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"}
• {"criterion_text":"- 7. History of other disease with poor prognosis"}
• {"criterion_text":"- 8. History of severe coronary heart disease (esp. after coronary artery bypass graft or history of myocardial infarction)or severe heart failure"}
• {"criterion_text":"- 9. Known HIV infection, active hepatitis B or C"}

Primary endpoints

• {"endpoint_text":"- Phase I: Incidence of dose-limiting toxicities (DLTs) during the first 8 weeks/56 days of MFA treatment.","definition_or_measurement_approach":"Incidence of DLTs observed during the first 8 weeks (56 days) of meclofenamate (MFA) treatment; safety/toxicity monitoring to determine recommended Phase II dose."}
• {"endpoint_text":"- Phase II: Progression-free survival (PFS) as measured from the day of randomization until diagnosis of progres-sive disease determined by MRI (RANO criteria) in the local center. In a sensitivity analysis, the PFS analysis does also include patients from phase I who received MFA at the same dose as applied in phase II (PFS measured from day of trial inclusion)","definition_or_measurement_approach":"PFS measured from day of randomization to progression as determined by local MRI using RANO criteria; sensitivity analysis includes phase I patients at same dose with PFS measured from inclusion."}

Secondary endpoints

• {"endpoint_text":"- Phase I: Progression-free survival (PFS) as measured from the inclusion into the trial until diagnosis of progressive disease determined by MRI (RANO criteria) in the local center.","definition_or_measurement_approach":"PFS measured from inclusion to progression by local MRI using RANO criteria."}
• {"endpoint_text":"- Phase I: Analysis of PFS according to post hoc central refer-ence neuroradiological assessment","definition_or_measurement_approach":"Central neuroradiological review post hoc to assess PFS."}
• {"endpoint_text":"- Phase I: Overall survival as measured from the day of inclusion into the trial","definition_or_measurement_approach":"Overall survival measured from inclusion date to death."}
• {"endpoint_text":"- Phase I: •Assessment of safety beyond 8 weeks MFA treat-ment: Toxicity, i.e. continuous monitoring of AE/SAE/SUSARs","definition_or_measurement_approach":"Continuous safety monitoring of adverse events (AE), serious adverse events (SAE), and SUSARs beyond 8 weeks of MFA treatment."}
• {"endpoint_text":"- Phase II: Analysis of PFS according to post hoc central refer-ence neuroradiological assessment. PFS analysis including both patients from phase II and patients from phase I who received MFA at the same dose as applied in phase II (PFS measured from day of trial inclusion).","definition_or_measurement_approach":"Central neuroradiological review for PFS; pooled analysis including phase I patients at same dose with PFS from inclusion."}
• {"endpoint_text":"- Phase II: Overall survival (OS) as measured from the day of randomization in phase II. A further sensitivity anal-ysis, will also include patients from phase I who re-ceived MFA at the same dose as applied in phase II. In these patients, OS starts from day of inclusion into the trial","definition_or_measurement_approach":"OS measured from randomization in phase II; sensitivity analysis includes phase I patients with OS from inclusion."}
• {"endpoint_text":"- Phase II: Assessment of safety: Toxcitiy, i.e. continuous moni-toring of AE/SAE/SUSARs until 3 days after end of therapy","definition_or_measurement_approach":"Continuous monitoring of AE/SAE/SUSARs until 3 days after end of therapy."}
• {"endpoint_text":"- Phase II: Karnofsky performance score (KPS), Quality of life (QoL) throughout the trial and Mini Mental state ex-amination (MMSE).","definition_or_measurement_approach":"Assessment of KPS, QoL instruments and MMSE at specified timepoints throughout the trial."}

Germany

Earliest CTIS Part Ii Submission Date

15-05-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

698

Number Of Sites

15

Number Of Participants

72

Primary sponsor

Full Name

Rheinische Friedrich-Wilhelms-Universitaet Bonn

Organisation Type

Educational Institution

Country Of Registered Address

Germany