C71
Conditions
Interventions
Group 1: Meclofenamate, oral administration, duration of treatment: 224 days or until tumor progression (what occurs first). Dosage 100mg - 400mg daily divided into two doses. Application additive to
Sponsors
Medizinische Fakultät der Universität BonnRheinische Friedrich-Wilhelms Universität Bonn
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: For Phase I and II 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. 2. Tumor progression according to RANO criteria 3. Written informed consent 4. Cognitive state to understand rationale and necessity of study therapy and procedures 5. MGMT promotor-methylated (MGMTmeth), IDH wildtype glioblastoma (GBM) or gliosarcoma confirmed with histology of the primary resection 6. Age > 18 years 7. Karnofsky performance score (KPS) =50%; 8. Life expectancy > 6 months 9. Adequate bone marrow reserve (WBC >3 G/nl, platelets >100 G/nl) 10. Adequate liver function (bilirubin <1.5 x ULN; ASAT /ALAT <3 x ULN, creatinine < 1.5 x ULN) 11. Patient compliance that allows adequate follow up 12. Male and female patients with reproductive potential must use an approved contraceptive method during and for 3 months after the trial (Pearl index <1%) 13. Pre-menopausal female patients with childbearing potential: a negative serum pregnancy test (beta-HCG) must be obtained prior to treatment start Additional criterion ONLY for phase I: 14. Resection at first relapse not yet performed; according to the local treating neurosurgeon and the documented decision of local neurooncological tumor board, reresection of the tumor is clinically indicated and can be safely deferred until day 7-10 after initiation of MFA/TMZ therapy.
Exclusion criteria
Exclusion criteria: For Phase I and II 1. Indication for hematotoxicity in first-line therapy not allowing TMZ starting dose 150 mg/m2/d at the discretion of the investigator 2. History of temozolomide-related liver toxicity > CTCAE5 grade 1 or skin toxicity > CTCAE5 grade 2 in first-line therapy 3. History of gastrointestinal bleeding or gastroduodenal ulcer, active gastritis 4. History of NSAID-related asthma, urticaria or allergic-type skin reactions 5. Uncontrolled malignancy within the last 2 years 6. History of confirmed or suspected hypersensitivity (delayed type and immediate type, inclusive of anaphylactic reaction) to any background/ standard TMZ drug product or one of its ingredients of the chosen product, or to cyclooxygenase inhibitors (“NSAIDs”), or to any ingredient of meclofenamate drug product 7. History of other disease with poor prognosis 8. Severe coronary heart disease (esp. after coronary artery bypass graft or history of myocardial infarction), severe heart failure 9. Known HIV infection, active hepatitis B or C 10. Breastfeeding or pregnant 11. Unable to undergo contrast-enhanced MRI (i.e. contrast allergy, implants, etc). 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 13. Medication with a drug that is not allowed in conjunction with MFA intake and cannot be discontinued: i.e. lithium, methotrexate, etc. 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 specified here: unfractionated heparin 7,500 IU BID or 5,000 IU TID; low molecular weight heparin e. g. enoxa-parin 40 mg/d; fondaparinux 2.5 mg/d; danaparoid sodium 750 IU BID; argatroban IV route thrombin time < 70 s; vitamin-K-antagonist INR < 1.8; dabigatran 150 mg BID; rivaroxaban 10 mg/d; edoxaban 30 mg/d; epixaban 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) 15. Patients with medically diagnosed hereditary Galactose Intolerance, complete lactase deficiency or confirmed Glucose-Galactose-Malabsortion 16. Medical History of gastrointestinal Resection of any kind that may potentially alter the absorption of the investigational study drug, according to investigators judgement 17. The presence of any other concomitant severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac (including 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Phase I: Incidence of dose-limiting toxicities (DLTs) during the first 8 weeks/56 days of MFA treatment. - Phase II: Progression-free survival (PFS) as measured from the day of randomization until diagnosis of progressive 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) | — |
Secondary
| Measure | Time frame |
|---|---|
| - 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; Overall survival as measured from the day of inclusion into the trial; Assessment of safety beyond 8 weeks MFA treatment: Toxicity, i.e. continuous monitoring of AE/SAE/SUSARs; Karnofsky performance score (KPS) and Quality of life (QoL) throughout the trial - Phase II: Analysis of PFS according to post hoc central reference 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); Overall survival (OS) as measured from the day of randomization in phase II. A further sensitivity analysis, will also include patients from phase I who received MFA at the same dose as applied in phase II. In these patients, OS starts from day of inclusion into the trial; Assessment of safety: continuous monitoring of AE/SAE/SUSARs until 30 days after end of therapy; Karnofsky performance score (KPS) and Quality of life (QoL) throughout the trial | — |
Countries
Germany
Contacts
Public ContactUlrich Herrlinger
Klinik für Neurologie und Zentrum für Integrierte OnkologieUniversität Bonn
Outcome results
None listed