Trial Design 

MONALISA will perform a prospective international randomized controlled pragmatic clinical trial. Prior to the start of the trial, patients can be asked to participate in a pre-screening phase where blood samples that are collected during this phase as part of routine biobanking practices, can be retrospectively included in the MONALISA database.  

The clinical trial will compare two different monitoring approaches: the current standard of care, which relies on imaging techniques and bone marrow assessments (according to INRC criteria), and a new approach based on liquid biopsy analysis, which analyses tumour markers in the blood (circulating DNA and mRNA). Both methods are important for understanding how best to monitor possible disease progression and ensure the most appropriate treatment for neuroblastoma. By comparing these two methods, we hope to find out if liquid biopsy can detect an event of relapse or disease progression earlier than standard of care, which could lead to earlier start of treatment and more personalized and targeted treatment options for children with neuroblastoma in the future. 

In 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). In Arm B, patients will only be monitored using standard of care techniques (every 3 to 6 months). 

Patient enrolment will take place within approximately 3.5 years. Each patient will be followed for maximally 18 months. If no event occurred after 18 months, we will collect standard of care information until a possible next event, or the end of MONALISA study, whichever comes first.    

The MONALISA Trial is expected to open in Summer 2025 in the Netherlands and in the end of 2025 in the other MONALISA countries. 

 

 

Population  

The study will enrol patients with high-risk neuroblastoma, from 6 months of age, with relapsed or refractory disease, that have received multiple lines of therapies.  

 

Inclusion criteria  

In order to be eligible to participate in this study, a patient must meet all of the following criteria:  

• Diagnosis of high-risk neuroblastoma  
• 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 event shows complete remission (CR), partial response (PR), mixed response (MR) or stable disease (SD) 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 patient’s age.

 

Exclusion criteria  

A patient who meets any of the following criteria will be excluded from participation in this study:  

• Participation in an experimental therapeutic clinical trial, where MONALISA trial randomisation methodology would impact clinical trial assessments of the therapeutic trial. Patients continuing treatment off experimental trial or on maintenance therapy post-trial are eligible for inclusion for the MONALISA trial when they meet all other criteria; 
• More than 3 months after ending relapse/refractory event therapy. This is to prevent bias in time to event as the likelihood of a new event increases over time. 

 

The MONALISA clinical trial sites 

 

I would like to open a trial site 

Contact point 

Clinical Trial Sponsor: Princes Maxima Center for Pediatric Oncology, Utrecht, The Netherlands 

Contact person: Prof. Lieve Tytgat monalisa@prinsesmaximacentrum.nl 

 

Monitoring Quality of Life (QoL) and Psychosocial Wellbeing with the MONALISA app 

To monitor the quality of life and psychosocial wellbeing of children with neuroblastoma and their families throughout the MONALISA study, a dedicated app was developed to collect electronic patient-reported outcomes (ePROs). Caregivers regularly complete standardised and custom-developed questionnaires via the MONALISA app. This app is connected to the MONALISA Dashboard for HCPs, a web-based platform, which allows healthcare professionals at the participating centres to access the questionnaire results in real time. 

 

The MONALISA app includes the following questionnaires: 

• Psychosocial Assessment Tool (PAT) 

to identify psychosocial risk factors in the family. 

• PedsQL Generic Core Scales and PedsQL Cancer Module 

to assess the health-related quality of life (HRQoL) of the child. 

• Weekly Symptom Screening 

to monitor key symptoms experienced by the child on a weekly basis using a custom-developed checklist.

• Patient Health Questionnaire-9 (PHQ-9) 

Generalised Anxiety Scale-7 (GAD-7) 
Fear of Cancer Recurrence Inventory – Parent Version (FCRI-P) 
Distress Thermometer for Parents (DT-P) 

to assess the psychosocial wellbeing of caregivers. 

• Evaluation Questionnaires – Study and MONALISA app 

to capture caregivers’ perspectives on the clinical study and their experience with the MONALISA app using custom-developed questionnaires. 

This short introductory video for caregivers offers further insight into the functionality of the MONALISA app.

Project partners involved in this work: Children’s Hospital “Agia Sofia” (Greece), Medical University Innsbruck (Austria), National and Kapodistrian University of Athens (Greece), Solving Kids’ Cancer (UK), Princess Máxima Center for Pediatric Oncology (The Netherlands), Evaluation Software Development (Austria).