Recurrent high-grade meningioma MedDRA version: 19.1 Level: PT Classification code 10027191 Term: Meningioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Yondelis 1 mg powder for concentrate for solution for infusion
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TR
Sponsors
European Organization for Research and Treatment of Cancer (EORTC)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ?Age 18 or older. ?Histological diagnosis of WHO grade II (chordoid meningioma, clear cell meningioma, atypical meningioma) or WHO grade III (papillary meningioma, rhabdoid meningioma, anaplastic/malignant meningioma) according to WHO 2007 classification. ?Radiologically documented progression of any existing tumor (growth > 25% in the last year) or appearance of new lesions (including intra- and extracranial manifestations). ?Measurable disease (10 x10 mm) on cranial MRI or CT thorax/abdomen no more than 2 weeks prior to randomization ?WHO performance status 0-2 ?Adequate liver, renal and hematological function within 2 weeks prior to randomization, defined as: ?Neutrophils = 1.5 x 109/L, hemoglobin = 9 g/dL or hemoglobin = 5.6 mmol/L, platelets = 100 x 109/L ?Total Bilirubin = ULN, SGPT/ALT and SGOT/AST = 2.5 x ULN ?Alkaline phosphatase = 2.5 x ULN; if alkaline phosphatase > 2.5 ULN, hepatic isoenzymes 5-nucleotidase or gamma glutyamyltransferase (GGT) must be within the normal range ?Albumin = 30 g/L ?Serum creatinine = 1.5 x ULN ?Creatinine clearance > 30 ml/min as calculated by Cockcroft and Gault formula (see Appendix E) ?Creatine phosphokinase (CPK) = 2.5 x ULN ?Normal cardiac function (LVEF assessed by MUGA or ECHO within normal range of the institution), normal 12 lead ECG (without clinically significant abnormalities). The following unstable cardiac conditions are not allowed: ?Congestive heart failure ?Angina pectoris ?Myocardial infarction within 1 year before registration/randomization ?Uncontrolled arterial hypertension defined as blood pressure = 150/100 mm Hg despite optimal medical therapy ?Arrhythmias clinically significant ?Life expectancy of at least 9 weeks Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior randomization (and again within 72 hours prior to to the first dose of study treatment). Patients of childbearing / reproductive potential should use adequate birth control measures, as defined below, during the study treatment period and for at least 3 months after the last study treatment. Men who are fertile must use effective contraception during treatment with trabectedin and for 5 months thereafter. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: ? combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: ? oral ? intravaginal ? transdermal ? progestogen-only hormonal contraception associated with inhibition of ovulation: ? oral ? injectable ? implantable ? intrauterine device (IUD) ? intrauterine hormone-releasing system ( IUS) ? bilateral tubal occlusion ? vasectomised partner ? sexual abstinence ? Acceptable birth control methods that result in a failure rate of more
Exclusion criteria
Exclusion criteria: ?More option for local therapy (resection or radiotherapy) after maximal feasible surgery and radiotherapy. ?Prior systemic anti-neoplastic therapy for meningioma (patient may have received prior radionuclide therapy). ?History of any other invasive malignancy within the last 5 years (except adequately treated non-melanoma skin cancer, clinicaly localized and very low risk prostate cancer, and adequately treated cervical intraepithelial neoplasia). ?Serious illness or medical conditions, specifically: active infectious process; chronic active liver disease, including chronic hepatitis B, C or cirrhosis. ? Concomitant use of any other investigational agent, phenytoin, or vaccination to yellow fever. ? Known hypersensitivity or contraindication to trabectedin or any of the ingredients of the trabectedin solution for infusion ? Known MRI or CT, including contrast media, contraindications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this randomized phase II study is to collect data on activity, safety and quality of life of trabectedin therapy in patients with recurrent high-grade meningioma.;Secondary Objective: The aim of this randomized phase II study is to collect data on activity, safety and quality of life of trabectedin therapy in patients with recurrent high-grade meningioma and to investigate whether trabectedin demonstrates sufficient antitumor activity against recurrent grade II or III to justify further investigation in phase III or as adjuvant therapy for newly diagnosed disease after resection and radiotherapy.;Primary end point(s): 1. Progression Free Survival (PFS);Timepoint(s) of evaluation of this end point: 1. PFS will be measured from the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first. Patients without evidence of progression will be censored at the last follow-up visit date. If a patient received a second anti-tumoral therapy without prior documentation of disease progression, the patient will be censored at the date of starting new anti-tumoral therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression Free Survival at 6 months (PFS-6), median PFS (mPFS) 2. Best overall response (BOR). Objective response (CR/PR), rate and median duration. Complete response (CR), rate and median duration. 3. Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median OS (mOS) 4. Safety (CTCAE v.4.0) 5. Health-related Quality of life (HRQol) ; Timepoint(s) of evaluation of this end point: 1.PFS-6 will be measured from the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first. 2.BOR will be measured from date of randomization until disease progression.CR/PR will be measured similar to PFS but starting from the time measurement criteria for CR/PR are first met. 3.From date of randomization up to the date of death (any cause).For patients still alive or lost to f/up at the time of analysis, survival will be censored at lastf/upvisitdate. 4.From the randomization until 30 days after last protocol treatment administration; or until the start of a new antitumor therapy. 5.At every scheduled visit, 4 weeks prior to randomization. | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical operations department
European Organization for Research and Treatment of Cancer (EORTC)
Outcome results
None listed