Trabectedin for Recurrent Grade II/III Meningioma

June 20, 2025 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Trabectedin for Recurrent Grade II or III Meningioma: a Randomized Phase II Study of the EORTC Brain Tumor Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a randomized open label multicenter comparative phase II trial. The objective of the study is 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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Linz, Austria
        • Landesnervenklinik Wagner Jauregg
      • Vienna, Austria
        • Medical University Vienna - General Hospital AKH
  • Belgium
      • Brussels, Belgium
        • Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
      • Edegem, Belgium
        • Universitair Ziekenhuis Antwerpen
      • Gent, Belgium
        • Universitair Ziekenhuis Gent
      • Leuven, Belgium
        • U.Z. Leuven - Campus Gasthuisberg
      • Yvoir, Belgium
        • CHU Dinant Godinne - UCL Namur
  • France
      • Bordeaux, France, 33075
        • CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
      • Bron, France
        • CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
      • Dijon, France
        • Centre Georges-Francois-Leclerc
      • Lille, France
        • CHRU de Lille
      • Lyon, France
        • Centre Léon Bérard
      • Montpellier, France
        • Institut régional du Cancer Montpellier
      • Nice, France
        • CHU de Nice - Hopital Pasteur
      • Paris, France
        • Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
      • Rennes, France
        • Centre Eugene Marquis
      • Villejuif, France
        • Gustave Roussy
  • Germany
      • Bonn, Germany
        • Universitaetsklinikum Bonn
      • Essen, Germany
        • Universitaetsklinikum - Essen
      • Frankfurt, Germany
        • Klinikum der J.W. Goethe Universitaet
      • Freiburg, Germany, 79106
        • Universitaetsklinikum Freiburg - Klinik fuer Neurochirurgie
      • Heidelberg, Germany, 69120
        • Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
      • Leipzig, Germany
        • Universitaetsklinikum Leipzig
      • Muenchen, Germany, 81377
        • Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern
      • Muenster, Germany
        • Universitaetsklinikum Muenster, Zentralklinikum
      • Regensburg, Germany
        • Universitaetskliniken Regensburg
      • Tubingen, Germany
        • Eberhard Karls Universitaet Tuebingen - Universitaetsklinikum Tuebingen
  • Italy
      • Milano, Italy
        • Ospedale San Raffaele
      • Milano, Italy
        • Fondazione IRCCS Istituto Neurologico Carlo Besta
      • Padova, Italy
        • Istituto Oncologico Veneto IRCCS - Ospedale Busonera
      • Roma, Italy
        • Istituto Regina Elena / Istituti Fisioterapici Ospitalieri
      • Torino, Italy
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Giovanni - Dipartimento Neuroscienze
  • Netherlands
      • Amsterdam, Netherlands
        • Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Rotterdam, Netherlands
        • Erasmus MC Cancer Institute - location Daniel den Hoed
  • Norway
      • Oslo, Norway
        • Oslo University Hospital - Radiumhospitalet
  • Spain
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Clinic Universitari de Barcelona
      • Barcelona, Spain
        • Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
      • L'Hospitalet de Llobregat, Spain
        • Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
  • Switzerland
      • Lausanne, Switzerland
        • Centre Hospitalier Universitaire Vaudois - Lausanne
      • Zurich, Switzerland
        • UniversitaetsSpital Zurich
  • United Kingdom
      • Bristol, United Kingdom
        • University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
      • Edinburgh, United Kingdom
        • NHS Lothian - Western General Hospital
      • London, United Kingdom
        • Guy's and St Thomas' NHS - St Thomas Hospital
      • Newcastle, United Kingdom
        • Newcastle Hospitals NHS Trust - Freeman Hospital, Northern Centre For Cancer Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Trabectedin
Patient will be treated with trabectedin
Drug: Trabectedin
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.
Other Names:
  • Yondelis
Other: Local standard of care
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
Left to the discretion of the investigator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival at 6 Months (PFS-6)
Time Frame: 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
The PFS probability at 6 months (PFS-6) was extracted from the Kaplan-Meyer PFS curve. 95% confidence intervals were computed based on the Greenwood's formula.
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)
Time Frame: 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.

Tumor response was measured according to the Macdonald response criteria as Complete Response (CR): disappearance of all target and non-target lesions. Residual lesions (other than nodes < 10 mm) thought to be non-malignant should be further investigated before CR can be accepted. Clinical evaluation must be stable or improving. No steroids should be needed.

Partial Response (PR): at least a 50% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non target lesions must be non-PD. Clinical evaluation must be stable or improving. Steroid dose must be stable or diminishing. Objective response was defined as both CR and PR. It was scheduled every 9 weeks from randomization until progression and after discontinuation of treatment without progression, every 9 weeks for the first year from randomization and every 12 weeks thereafter.
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)
Time Frame: 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.
Overall Survival (OS) was calculated from the date of randomization up to the date of death (any cause). For patients still alive or lost to follow-up at the time of analysis, survival will be censored at last follow-up visit date.
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)
Time Frame: 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.
Due to the small sample size and low compliance in the Standard of Care (SoC) arm, the analysis of Quality of Life (QoL) was restricted to describing The Global health status / QoL scores at baseline. The Global health status / QoL scores are part of the EORTC QLQ-C30, which is a core questionnaire designed to assess the quality of life of cancer patients. These scores are derived from a specific scale within the EORTC Quality of Life Questionnaire (QLQ-C30) that evaluates the overall health status and quality of life of the patient. The scoring for the Global health status / QoL scale involves a linear transformation of the raw score to a standardized score ranging from 0 to 100. This scale is revised in version 3.0 of the QLQ-C30 and includes two items with a range of 6, specifically items 29 (Global health status)and 30 (QoL scale). Higher score values represent a better outcome i.e. a higher quality of life.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Matthias Preusser, Medical University Vienna - General Hospital AKH

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

July 1, 2017

Study Completion (Actual)

January 16, 2019

Study Registration Dates

First Submitted

August 7, 2014

First Submitted That Met QC Criteria

September 4, 2014

First Posted (Estimated)

September 9, 2014

Study Record Updates

Last Update Posted (Actual)

July 10, 2025

Last Update Submitted That Met QC Criteria

June 20, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-1320-BTG
  • 2014-002446-47 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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