MONALISA – A SIOPEN Study to MOnitor NeuroblastomA relapse with LIquid biopsy Sensitive Analysis
Coordinating investigator(s)/project leader(s): Prof. Dr. Lieve Tytgat (MAXIMA) and Dr. Sabine Taschner-Mandl (CCRI)
Sponsor: Princes Maxima Centrum, Utrecht, The Netherlands
Funders / Charity: Funded by the European Union (European Health and Digital Executive Agency (HaDEA)) under the EU Cancer Mission - Grant Agreement number 101137028
MONALISA is a European collaborative clinical trial coordinated by the Princes Máxima Center for Pediatric Oncology (MÁXIMA, the Netherlands) and St. Anna Children’s Cancer Research Institute (CCRI, Austria), counting with the long-term collaborative network of SIOPEN and its members. The clinical trial is partially financed under the framework of an EU-funded project coordinated by SIOP EUROPE.
MONALISA is conducting a pragmatic clinical trial to evaluate the use of liquid biopsies as a monitoring tool for relapsed neuroblastoma. We will test if liquid biopsies can detect relapse events earlier than the standard of care and consequently avoid unnecessary diagnostic procedures. This approach will also help to personalize treatment options and may prevent both over- and under-treatment. Ultimately, the goal is to improve the quality of life of affected children by enabling earlier, accurate tumour detection and hopefully better overall survival through more targeted treatment interventions.
Aims of the study
Monitor patients with relapsed neuroblastoma
Reliable assessment of early molecular progression or relapse
Establish a pragmatic randomized clinical trial
Develop a digital decision support tool to help oncologists use the new monitoring
Assess patient-reported outcomes and quality of life
Study design
MONALISA is a prospective international randomized controlled pragmatic clinical trial enrolling patients aged from 6 months of age, diagnosed with HR Neuroblastoma with relapse or refractory disease who have received multiple lines of therapies.
Patient eligibility
Initial diagnosis of high-risk neuroblastoma as per SIOPEN modified INRG staging system
From 6 months of age
After initiation of second-line (or third- or fourth-line) therapy for relapsed or refractory disease
Most recent evaluations after therapy for the event show complete remission, partial response, mixed response or stable disease for at least 2 months, as per local disease assessment defined according to the INRC criteria
Written informed consent of both caregivers/legal representatives and/or patients, according to the patient’s age
Treatment Arms
Arm A: Patients will have monthly liquid biopsies with real-time analysis and reporting to clinicians, as well as the standard of care monitoring (every 3 to 6 months).
Arm B: Patients will only be monitored using standard of care techniques (every 3 to 6 months).
Each patient will be followed for a maximum of 18 months.
Outcome Measures/Questions to be answered:
Primary objective: To investigate whether liquid biopsies may detect relapse or progression (defined as a molecular event) earlier than standard-of-care disease assessment (defined as clinical event), through either the appearance of a new liquid biopsy signal or an increase in a pre-existing liquid biopsy signal.
Secondary objectives:
To estimate and compare overall survival (OS) between patients with monthly liquid biopsy follow-up and 6 monthly standard of care disease assessment
To validate the use of liquid biopsies to detect an event, and the clinical acceptance and satisfaction of both patients and clinicians
To measure the change in care initiated by liquid biopsy results indicative of an event
To establish the potential use of liquid biopsies in risk stratification and in identifying patients suitable for targeted therapy
To assess whether liquid biopsy testing can be implemented as a clinical standard of care diagnostic in all study countries
To assess the technical and clinical cut-off values for positivity in liquid biopsy testing
To establish the effect of minimally invasive diagnostics of liquid biopsies on Health-related Quality of Life
To evaluate the usability and feasibility of Patient Reported Outcomes (PRO) and Observer Reported Outcome (ObsRO) assessments in paediatric clinical trials with weekly symptom monitoring via a mobile device application
To assess socioeconomical inequities in access to and participation in clinical trials
To evaluate the change in weekly symptoms over time for the on-trial population and investigate possible differences between the two trial arms
Current study status
Start date: expected November 2025
Recruitment period: 3 years
Estimated completion: End of 2028
Expected recruitment: 15 patients
Actual recruitment: start planned by Dec-2025
STATUS OF MONALISA TRIAL: In SET-UP
Coordinating Centres
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
St. Anna Children’s Cancer Research Institute, Vienna, Austria
Participating Centres
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
St. Anna Children’s Cancer Research Institute, Vienna, Austria
Ghent University, Ghent, Belgium
Motol University Hospital, Prague, Czech Republic
Gustave Roussy Institute, Paris, France
Institute Curie, Paris, France
Charité – University Medicine Berlin, Berlin, Germany
University of Tübingen, Tübingen, Germany
Agia Sofia Children’s Hospital, Athens, Greece
Children’s Health Ireland, Dublin, Ireland
Giannina Gaslini Institute, Genoa, Italy,
Vall d’Hebron Barcelona Hospital Foundation, Barcelona, Spain
Institute of Cancer Research: the Royal Cancer Hospital LBG, London, UK
Funding and Support
European Union Horizon Europe Programme – Topic HORIZON-MISS-2023-CANCER-01-03, Grant Agreement number 101137028
CONSORTIUM
25 leading European institutions including academic research institutes, clinical centres, diagnostic laboratories, social sciences experts, technology providers and patient advocates have joined forces for MONALISA, an EU project funded by Horizon Europe.
