Clinical trial NCT02234050: Trabectedin for Recurrent Grade II/III Meningioma
Official title: Trabectedin for Recurrent Grade II or III Meningioma: a Randomized Phase II Study of the EORTC Brain Tumor Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2014-09-09
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Patient selection 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)
* 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 ULN, SGPT/ALT and SGOT/AST ≤ 2.5 x ULN
  * Alkaline phosphatase ≤ 2.5 x ULN; if alkaline phosphatase \> 2.5 ULN, ALP hepatic isoenzyme and/or 5-nucleotidase and/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
* No 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)
* 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 ICH/GCP, and national/local regulations.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first
Secondary outcomes:
measure: Progression Free Survival at 6 months (PFS-6), median PFS (mPFS)
timeFrame: From the date of randomization until the date of first objective progression or the date of patient's death whichever occurs first
measure: Best overall response (BOR). Objective response (CR/PR), rate and median duration. Complete response (CR), rate and median duration.
timeFrame: From the date of randomization until disease progression
measure: Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median OS (mOS)
timeFrame: From the date of randomization up to the date of death, up to 12 months
measure: Safety (CTCAE v.4.0)
timeFrame: From randomization up to 30 days after administration of the last dose of protocol treatment or until the start of a new antitumor therapy, whichever occurs first.
measure: Health-related Quality of life (HRQol)
timeFrame: Untill six months after randomization
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Landesnervenklinik Wagner Jauregg
city: Vienna
country: Austria
facility: Medical University Vienna - General Hospital AKH
city: Brussels
country: Belgium
facility: Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne - UCL Namur
city: Bordeaux
country: France
facility: CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
city: Bron
country: France
facility: CHU de Lyon - CHU Lyon - Hopital neurologique Pierre Wertheimer
city: Dijon
country: France
facility: Centre Georges-Francois-Leclerc
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Nice
country: France
facility: CHU de Nice - Hopital Pasteur
city: Paris
country: France
facility: Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Villejuif
country: France
facility: Gustave Roussy
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Essen
country: Germany
facility: Universitaetsklinikum - Essen
city: Frankfurt
country: Germany
facility: Klinikum Der J.W. Goethe Universitaet
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg - Klinik fuer Neurochirurgie
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg - UniversitaetsKlinikum Heidelberg - Head Hospital
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Muenchen
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster, Zentralklinikum
city: Regensburg
country: Germany
facility: Universitaetskliniken Regensburg
city: Tubingen
country: Germany
facility: Eberhard Karls Universitaet Tuebingen - Universitaetsklinikum Tuebingen
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS - Ospedale Busonera
city: Roma
country: Italy
facility: Istituto Regina Elena / Istituti Fisioterapici Ospitalieri
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino - Ospedale San Giovanni - Dipartimento Neuroscienze
city: Amsterdam
country: Netherlands
facility: Spaarne Gasthuis - Vrije Universiteit Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute - location Daniel den Hoed
city: Oslo
country: Norway
facility: Oslo University Hospital - Radiumhospitalet
city: Barcelona
country: Spain
facility: Hospital Clinic Universitari de Barcelona
city: Barcelona
country: Spain
facility: Hospital De La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia - ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois - Lausanne
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zurich
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Western General Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS - St Thomas Hospital
city: Newcastle
country: United Kingdom
facility: Newcastle Hospitals NHS Trust - Freeman Hospital, Northern Centre For Cancer Care
Study officials:
affiliation: Medical University Vienna - General Hospital AKH
name: Matthias Preusser
role: STUDY_CHAIR
References:
citation: 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.