Clinical trial NCT04253015: A Post-Authorisation Safety Study Patient Registry of Patients With Neuroblastoma Being Treated With Dinutuximab Beta
Official title: A Post-Authorisation Safety Study Patient Registry of Patients With High-risk Neuroblastoma Being Treated With the Monoclonal Antibody Dinutuximab Beta
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neuroblastoma
Keywords: Tumour
Brain tumour
Paediatrics
Lead sponsor: RECORDATI GROUP
Sponsor class: INDUSTRY
Collaborators: name: United BioSource, LLC
First posted: 2020-02-05
Enrollment: 125
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with high-risk neuroblastoma who are starting treatment with dinutuximab beta in the standard clinical practice setting or participating in a clinical trial where dinutuximab beta is provided according to the indication as per the country/regional marketing authorisation, provide consent/assent and are willing to be followed up for up to 10 years. Centers who treat neuroblastoma patients with dinutuximab beta will be invited to participate in the registry. This includes networks such as the Society of Paediatric Oncology for the Treatment of Neuroblastoma (SIOPEN) in Europe.

Brief summary: This is a non-interventional, multi-national, observational, prospective patient registry to further evaluate the effectiveness and safety of dinutuximab beta - a monoclonal immunoglobulin G 1 (IgG1) antibody, to obtain information on survival, pain severity and incidence of neuro-toxicity, visual impairment, capillary leak syndrome, cardiovascular events, hypersensitivity reactions and long-term safety.

Detailed description: Rationale and Background:

Neuroblastoma, is the most common extra-cranial solid tumour in children. Most patients with neuroblastoma are diagnosed under the age of 5 years and most present with metastatic disease and/or high-risk features. Despite the introduction of novel treatment strategies, including high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), the outcome of these patients remains poor.

Dinutuximab beta is a chimeric monoclonal immunoglobulin G 1 (IgG1) antibody that is specifically directed against the carbohydrate moiety of disialoganglioside antigen (GD2), which is overexpressed on neuroblastoma cells. By binding to neuroblastoma cells, dinutuximab beta can induce both complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC).

The efficacy of dinutuximab beta has been evaluated in a randomised controlled trial comparing the administration of dinutuximab beta with or without interleukin 2 (IL-2) in the first-line treatment of patients with high-risk neuroblastoma and in two singlearm studies in the relapsed/refractory setting. The efficacy and safety of dinutuximab beta will further be evaluated in this registry that will provide information on survival, pain severity and incidence of neurotoxicity, visual impairment, capillary leak syndrome, cardiovascular events, hypersensitivity reactions and long-term safety.

Study Design:

This is a non-interventional, multi-national, observational, prospective patient registry of patients with high-risk neuroblastoma being treated with the monoclonal antibody dinutuximab beta. The efficacy and safety of dinutuximab beta will further be evaluated in this registry that will provide information on survival, pain severity and incidence of neurotoxicity, visual impairment, capillary leak syndrome, cardiovascular events, hypersensitivity reactions and long-term safety.

Research Questions and Objectives:

Primary objectives:

* To assess pain severity and use of analgesics during the period of first dose of dinutuximab beta to end of last 35 day course of the 5th cycle of treatment
* To assess the incidence of neurotoxicity, visual impairment, capillary leak syndrome, cardiovascular events and hypersensitivity reactions
* To assess the long term safety profile

Secondary objectives:

* Progression free survival (PFS) in patients treated with dinutuximab beta.
* Event Free Survival (EFS) in patients treated with dinutuximab beta
* Overall survival (OS) in patients treated with dinutuximab beta

Population:

Patients diagnosed with high-risk neuroblastoma who are starting treatment with dinutuximab beta in the standard clinical practice setting or participating in a clinical trial where dinutuximab beta is provided according to the indication as per the country/regional marketing authorisation, provide consent/assent and are willing to be followed up for up to 10 years.

Study Size:

It is planned to enroll a sufficient number of patients (estimated at 125) such that 100 patients will have completed all five treatment courses of dinutuximab beta. It is anticipated that this will result in 40-50 patients who are progression free at 10 years.

Data Sources:

Data will be collected from physicians using an electronic data capture (EDC) system. The electronic case report forms (eCRFs) will be designed to gather data from the medical records at baseline, during treatment and at normal clinical practice follow up visits.

Data Analysis:

The safety analysis set, containing all patients treated with at least one dose of dinutuximab beta will be considered for safety and efficacy analyses. All baseline, treatment period and follow up characteristics will be summarized using descriptive statistics. Endpoints addressing primary and secondary analysis will include 95% confidence intervals (CIs) including the Clopper Pearson method for binomial, log-log transform for survival. OS, PFS and EFS will be analysed using Kaplan-Meier methods.

Variables:

Baseline (prior to start of treatment): Demographics, clinical trial participation, neuroblastoma disease history, and presence or absence of neurotoxicity, visual impairment, and cardiovascular abnormality.

Treatment period (up to end of last 35 day course of 5th cycle of treatment):

Dosing regimen, total cumulative amount of dinutuximab beta per course, concomitant medications during course (IL-2, retinoic acid and/or antihistamines), daily analgesics (opioids, gabapentin/ pregabalin and/or non-opioid analgesics and other neuropathic pain treatments), daily pain assessment during infusion of dinutuximab beta, occurrence of neurotoxicity, visual impairment, capillary leak syndrome, cardiovascular events, and hypersensitivity reactions, adverse events (AEs)/serious adverse events (SAEs) treatment interruptions and discontinuations, progression of disease, date and cause of death, reason for study withdrawal (if applicable) Follow up (from end of last 35 day course of 5th cycle of treatment): Status of neurotoxicity, visual impairment, cardiovascular events, (resolved, not resolved), SAEs and adverse drug reaction (ADRs), progression of disease, date and cause of death, reason for study withdrawal (if applicable).

Eligibility criteria: Inclusion Criteria:

Patients meeting the following criteria will be considered for inclusion into the registry:

* Patients diagnosed with high-risk neuroblastoma and starting treatment with commercially available dinutuximab beta OR
* Patients diagnosed with high-risk neuroblastoma and starting treatment with dinutuximab beta in a clinical trial where dinutuximab beta is provided according to the country/regional marketing authorisation AND
* Appropriate consent/assent has been obtained for participation in the registry with a willingness to be followed up for up to 10 years.

Exclusion Criteria:

Patient will not be eligible for inclusion if the following criterion applies:

* Patients commencing dinutuximab beta within a clinical trial where the product is being provided outside of the country/regional marketing authorisation OR
* Appropriate consent/assent has not been obtained for participation in the registry or patient/legal representative is not willing for the patient be followed up for up to 10 years.

Primary outcomes:
measure: Assessment of the severity of pain experienced by participants during treatment with dinutuximab beta
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
measure: Number of participants using analgesics during treatment with dinutuximab beta
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
measure: Incidence of neurotoxicity, visual impairment, capillary leak syndrome, cardiovascular events and hypersensitivity reactions
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
measure: Number of participants experiencing serious adverse events (SAEs) and adverse drug reactions (ADRs) during treatment with dinutuximab beta
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
measure: Progression free survival (PFS)
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
measure: Event Free Survival (EFS)
timeFrame: First dose of dinutuximab beta to the end of the last 35 day course of the 5th cycle of treatment (each cycle is 35 days)
Other outcomes:
Locations:
city: Wien,
country: Austria
facility: St. Anna Kinderkrebsforschung
state: Vienna
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Hôpital de la Timone, Hôpital des Enfants
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charité Berlin
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Kraków
country: Poland
facility: Uniwersytecki Szpital Dziecięcy
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe Avenida Fernando Abril Martorell
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals NHS Foundation Trust
state: Newcastle
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
affiliation: EUSA Pharma (UK) Limited
name: Jose-Luis Garcia
role: STUDY_DIRECTOR
References: