2024-511264-89-00招募中2 期
Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy (MecMeth/ NOA-24)
Rheinische Friedrich-Wilhelms-Universitaet Bonn15 个研究点 分布在 1 个国家目标入组 72 人开始时间: 2024年5月24日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 15
- 主要终点
- Phase I: Incidence of dose-limiting toxicities (DLTs) during the first 8 weeks/56 days of MFA treatment.
研究概览
简要总结
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.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •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 and geographic proximity that allow 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:
- •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) ≥60%;
- •Life expectancy > 6 months
- •Adequate bone marrow reserve (WBC >3 G/nl, platelets >100 G/nl
排除标准
- •Indication for hematotoxicity in first-line therapy not allowing TMZ starting dose 150 mg/m2/d
- •Breastfeeding or pregnant
- •Unable to undergo contrast-enhanced MRI (i.e. contrast allergy, implants, etc
- •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
- •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
- •Patients with medically diagnosed hereditary Galactose Intolerance, com-plete lactase deficiency or confirmed Glucose-Galactose-Malabsorption
- •Medical History of gastrointestinal Resection of any kind that may poten-tially alter the absorption of the investigational study drug, according to investigators judgement
- •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
- •History of skin or liver toxicity >CTCAE5 grade 1 in first-line therapy
- •History of gastrointestinal bleeding or gastroduodenal ulcer, active gastritis
- •History of asthma, urticaria or allergic-type skin reactions to NSAID
- •Prior malignancy other than glioma
- •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 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
结局指标
主要结局
Phase I: Incidence of dose-limiting toxicities (DLTs) during the first 8 weeks/56 days of MFA treatment.
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 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)
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)
次要结局
- 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.
- Phase I: Analysis of PFS according to post hoc central refer-ence neuroradiological assessment
- Phase I: Overall survival as measured from the day of inclusion into the trial
- Phase I: •Assessment of safety beyond 8 weeks MFA treat-ment: Toxicity, i.e. continuous monitoring of AE/SAE/SUSARs
- 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).
- 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
- Phase II: Assessment of safety: Toxcitiy, i.e. continuous moni-toring of AE/SAE/SUSARs until 3 days after end of therapy
- Phase II: Karnofsky performance score (KPS), Quality of life (QoL) throughout the trial and Mini Mental state ex-amination (MMSE).
研究者
Prof. Dr. Ulrich Herrlinger
Scientific
Rheinische Friedrich-Wilhelms-Universitaet Bonn
研究点 (15)
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