Adult patients with IDHwt, MGMT promotor methylated glioblastoma at first relapse MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Meclofenamate sodium
Pharmaceutical Form: Capsule
INN or Proposed INN: MECLOFENAMATE SODIUM
CAS Number: 6385-02-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Rheinische Friedrich-Wilhelms-Universität Bonn
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 radiothera-py 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 con-firmed with histology of the primary resection or, in phase II, last resection 6. age > 18 years 7. Karnofsky performance score (KPS) =60%; 8. Life expectancy > 6 months 9. Adequate bone marrow reserve (WBC >3 G/nl, platelets >100 G/nl) 10. Adequate liver function (bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Indication for hematotoxicity in first-line therapy not allowing TMZ starting dose 150 mg/m2/d 2. History of skin or liver toxicity >CTCAE5 grade 1 in first-line therapy 3. History of gastrointestinal bleeding or gastroduodenal ulcer, active gastritis 4. History of asthma, urticaria or allergic-type skin reactions to NSAID 5. Prior malignancy other than glioma 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 disease with poor prognosis 8. History of severe coronary heart disease (esp. after coronary artery bypass graft or history of myocardial infarction) or 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 investiga-tional 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 discontin-ued: 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 throm-bin time < 70 s; dabigatran 110 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 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 |
|---|---|
| Main Objective: 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.;Secondary Objective: To determine the efficacy of meclofenamate sodium therapy in addition to standard temozolomide throughout the trial. To assess the safety and tolerability of meclofenamate sodium therapy in addition to standard temozolomide throughout the trial. To evaluate the clinical effect of meclofenamate sodium therapy in addition to temozolomide and the development of quality of life throughout the trial. ;Primary end point(s): Incidence of dose-limiting toxicities (DLTs, Phase I) and Progression-free survival (PFS, Phase II);Timepoint(s) of evaluation of this end point: After 56 days of meclofenamate sodium treatment (DLT incidence) and at diagnosis of progressive disease determined by MRI (RANO criteria) in the local center (PFS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: Progression-free survival (PFS); Overall survival (OS); Assessment of safety beyond 8 weeks MFA treatment: Toxicity, i.e. continuous monitoring of AE/SAE/SUSARs; Karnofsky performance score (KPS), Quality of life (QoL) and Mini-Mental-status examination (MMSE). Phase II: PFS according to post hoc central reference neuroradiological assessment; OS; Assessment of safety: Toxicity, i.e. continuous monitoring of AE/SAE/SUSARs; KPS, QoL and MMSE.;Timepoint(s) of evaluation of this end point: Phase I: PFS is measured at diagnosis of progressive disease determined by MRI (RANO criteria) in the local center and according to post hoc central reference neuroradiological assessment; OS is measured from the day of inclusion into the trial; Safety is measured until 3 days after end of therapy; KPS, QoL and MMSE are measured throughout the trial. Phase II: PFS is measured post hoc at the central reference neuroradiological assessment; OS is measured from the day of randomization in phase II; Safety is measured until 3 days after end of therapy; KPS, QoL and MMSE are measured throughout the trial. | — |
Countries
Germany
Contacts
Public ContactCorinna Reineke
Studienzentrale Studienzentrum Bonn (SZB)
Outcome results
None listed