Trabectedin for Recurrent Grade II/III Meningioma

NCT02234050 | Completed Phase 2 Results DMC

• 2 other identifiers: EORTC-1320-BTG2014-002446-47
• Study Type: interventional
• Target: 90
• Locations: 10 countries
• Sites: 47

Brief Summary

The aim of this study is to collect data on activity, toxicity and quality of life of trabectedin therapy in patients with recurrent high-grade meningioma.

Conditions

Recurrent High Grade Meningioma

Keywords

Grade 2 Chordoid meningioma; Grade 2 Clear cell meningioma; Grade 2 Atypical meningioma; Grade 3 Papillary meningioma; Grade 3 Rhabdoid meningioma; Grade 3 Anaplastic meningioma; Grade 3 Malignant meningioma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression (PD) was measured according to the Macdonald response criteria as at least a 25% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥ 5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas). Progression Free Survival (PFS) was 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 was 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 was censored at the date of starting new anti-tumoral therapy.

  From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first up.PFS was assessed by its median the point time at which 50% of the patients have experienced disease progression or death.

Secondary Outcomes (4)

• Progression Free Survival at 6 Months (PFS-6)

  From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first. PFS at 6 months,the proportion of patients who have not experienced disease progression or death by 6 months is presented

• Objective Response (CR/PR)

  From the date of randomization until disease progression or death, up to 24 months from date of randomization.It was assessed every 9 or 12 weeks (see measure description for details).The response rate presented is based on the best response observed.

• Overall Survival (OS)

  From the date of randomization up to the date of death. OS was assessed by its median the point time at which 50% of the patients have experienced death.

• Health-related Quality of Life (HRQol)

  Baseline measurements were collected before or on the day of the start of protocol treatment, but no earlier than 28 days before. The median baseline Global health status / QoL scores per treatment arm is reported.

Study Arms (2)

Trabectedin

EXPERIMENTAL

Patient will be treated with trabectedin

Drug: Trabectedin

Local standard of care

OTHER

Treatment in the control arm is left to the discretion of the investigator, according to the local standard of care.

Other: Local standard of care

Interventions

Trabectedin DRUG

Trabectedin will be given as a 24-hour infusion every 3 weeks at a starting dose of 1.5 mg/m2 body surface area (BSA), until one of the treatment withdrawal criteria has been met.

Also known as: Yondelis

Trabectedin

Local standard of care OTHER

Left to the discretion of the investigator

Local standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Patient selection criteria * Age 18 or older * Histological diagnosis of World Health Organization (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) * No more option for local therapy (resection or radiotherapy) after maximal feasible surgery and radiotherapy * No prior systemic anti-neoplastic therapy for meningioma * Measurable disease (10 x10 mm) on cranial MRI no more than 2 weeks prior to randomization. * WHO performance status 0-2 * Adequate liver, renal and hematological function within 4 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 ≤ 1 x Upper Limit of Normal (ULN), serum glutamate pyruvate transaminase(SGPT)/ Alanine Aminotransferase (ALT) and serum glutamate oxaloacetate transaminase (SGOT)/ Aspartate Aminotransferase (AST) ≤ 2.5 x ULN * Alkaline phosphatase ≤ 2.5 x ULN; if alkaline phosphatase \> 2.5 ULN, Alkaline Phosphatase (ALP) hepatic isoenzyme and/or 5-nucleotidase and/or gamma glutamyltransferase (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 Multigated radionuclide angiography (MUGA) or Echocardiogram (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 * No history of any other invasive malignancy within the last 5 years (except adequately treated non-melanoma skin cancer, clinically localized and very low risk prostate cancer, and adequately treated cervical intraepithelial neoplasia) * No serious illness or medical conditions, specifically: active infectious process; chronic active liver disease, including chronic hepatitis B, C or cirrhosis * No concomitant use of any other investigational agent or phenytoin * Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. Women 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 that results in low failure rate, i.e. less than 1% per year, when used consistently and correctly. * Female subjects who are breastfeeding should discontinue nursing prior to the first dose of study treatment and until 3 months after the last study treatment. * No known MRI or CT, including contrast media, contraindications * 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 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)/ Good Clinical Practice (GCP), and national/local regulations.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (47)

Landesnervenklinik Wagner Jauregg

Linz, Austria

Location

Medical University Vienna - General Hospital AKH

Vienna, Austria

Location

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

CHU Dinant Godinne - UCL Namur

Yvoir, Belgium

Location

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, 33075, France

Location

CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer

Bron, France

Location

Centre Georges-Francois-Leclerc

Dijon, France

Location

CHRU de Lille

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Institut régional du Cancer Montpellier

Montpellier, France

Location

CHU de Nice - Hopital Pasteur

Nice, France

Location

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, France

Location

Centre Eugene Marquis

Rennes, France

Location

Gustave Roussy

Villejuif, France

Location

Universitaetsklinikum Bonn

Bonn, Germany

Location

Universitaetsklinikum - Essen

Essen, Germany

Location

Klinikum Der J.W. Goethe Universitaet

Frankfurt, Germany

Location

Universitaetsklinikum Freiburg - Klinik fuer Neurochirurgie

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, Germany

Location

Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern

München, 81377, Germany

Location

Universitaetsklinikum Muenster, Zentralklinikum

Münster, Germany

Location

Universitaetskliniken Regensburg

Regensburg, Germany

Location

Eberhard Karls Universitaet Tuebingen - Universitaetsklinikum Tuebingen

Tübingen, Germany

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Istituto Oncologico Veneto IRCCS - Ospedale Busonera

Padua, Italy

Location

Istituto Regina Elena / Istituti Fisioterapici Ospitalieri

Roma, Italy

Location

Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Giovanni - Dipartimento Neuroscienze

Torino, Italy

Location

Spaarne Gasthuis - Vrije Universiteit Medisch Centrum

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Erasmus MC Cancer Institute - location Daniel den Hoed

Rotterdam, Netherlands

Location

Oslo University Hospital - Radiumhospitalet

Oslo, Norway

Location

Hospital Clinic Universitari de Barcelona

Barcelona, Spain

Location

Hospital De La Santa Creu I Sant Pau

Barcelona, Spain

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Barcelona, Spain

Location

Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

L'Hospitalet de Llobregat, Spain

Location

Hospital Universitario 12 De Octubre

Madrid, Spain

Location

Centre Hospitalier Universitaire Vaudois - Lausanne

Lausanne, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, Switzerland

Location

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre

Bristol, United Kingdom

Location

NHS Lothian - Western General Hospital

Edinburgh, United Kingdom

Location

Guy's and St Thomas' NHS - St Thomas Hospital

London, United Kingdom

Location

Newcastle Hospitals NHS Trust - Freeman Hospital, Northern Centre For Cancer Care

Newcastle, United Kingdom

Location

Related Publications (1)

• Hundsberger T, Surbeck W, Hader C, Putora PM, Conen K, Roelcke U. [Meningioma: management of the most common brain tumour]. Praxis (Bern 1994). 2016 Apr 13;105(8):445-51. doi: 10.1024/1661-8157/a002320. German.

  PMID: 27078728 DERIVED

MeSH Terms

Interventions

Trabectedin

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Thierry Gorlia
• Organization: EORTC

thierry.gorlia@eortc.org

027741652

Study Officials

• Matthias Preusser

  Medical University Vienna - General Hospital AKH

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: September 9, 2014
• Study Start: July 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: January 16, 2019
• Last Updated: July 10, 2025
• Results First Posted: July 10, 2025

Record last verified: 2025-06

Locations

NO (1); ES (5); DE (10); GB (4); CH (2); IT (5); FR (10); BE (5); NL (3); AU (2)