Trabectedin for recurrent grade II or III meningioma: a randomized phase II study of the EORTC Brain Tumor Group.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 3

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 to randomization and again within 72 hours prior to the first dose of study treatment. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, 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. A highly effective method of birth control is defined as one which results in low failure rate, i.e. less than 1% per year, when used consistently and correctly.
*Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment.
*Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
*Patients with a buffer range from the normal values of +/- 5 % for hematology and +/- 10% for biochemistry are acceptable. A maximum of +/- 2 days for timelines may be acceptable
*Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

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 or phenytoin.;*Known MRI or CT, including contrast media, contraindications.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>* Progression Free Survival (PFS)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Progression Free Survival at 6 months (PFS-6), median PFS (mPFS)<br /><br>* Best overall response (BOR). Objective response (CR/PR), rate and median<br /><br>duration. Complete response (CR), rate and median duration.<br /><br>* Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median<br /><br>OS (mOS)<br /><br>* Safety (CTCAE v.4.0)<br /><br>* Health-related Quality of life (Qol)</p><br>