Investigator-initiated multinational early-stage innovative clinical trials for paediatric cancer

This topic will contribute to the achievement of the Mission’s objective to provide better treatments for cancer. The focus is on children (0-14 years of age, e.g. age of first cancer diagnosis) and/or adolescent (15-19 years of age, e.g. age of first cancer diagnosis) cancer patients.

Paediatric oncology has made considerable progress, increasing patient survival rates up to 80%; yet cancer remains the leading cause of death in children and adolescents. Progress in R&I to support the development of targeted cancer treatments for children has been rather limited. Over the past 20 years, less than 10% of new anti-cancer drugs have received marketing authorization for paediatric use, resulting in limited availability of innovative therapies to treat paediatric cancers. This is even more striking when cancers with poor prognosis are considered.

Most of the treatments currently used for paediatric cancers have been developed to treat adult cancers; in addition, young cancer patients and survivors very often experience adverse late-effects[[ Late-effects range from cardiovascular disease, organ and skin alterations, fertility problems, cognitive impairment, and mental health issues such as depression and anxiety etc. The 2024 Cancer Mission annual work programme includes a topic (HORIZON-MISS-2024-CANCER-01-05) to improve the understanding and management of late-effects in Adolescent and Young Adults, cancer patients and survivors]] due to the high toxicity of treatments. Clinical tools used to evaluate treatment outcomes (e.g. tools to assess toxicity, radiological response, quality of life etc.), are also derived from adult oncology and therefore suboptimal;

This situation mostly reflects the fact that paediatric cancers are rare, and their biology is different to adult cancers. The relatively low number of cases warrants the implementation of multinational academic-initiated clinical trials to accelerate the development of innovative, more effective and less toxic treatments.

Proposals should address all of the following:

• Design and conduct innovative investigator-initiated multinational early-stage clinical trials, (phase 1 and 1/2) to accelerate the development of safe, effective, targeted cancer treatments[[Including but not limited to new and repurposed drugs, innovative radiation and immunotherapy approaches, advanced therapies, combination of treatments and/or with other interventions etc]] for children and/or adolescents with cancer. Focus should be on cancers with poor prognosis (e.g. with a 5-year overall survival less than 50% from time of diagnosis) at any stage of the disease and for any type. Trials should take into account socio-economic and biological stratification. All data should be disaggregated by sex, gender, age and other relevant variables;
• Develop innovative clinical tools (companion diagnostics) to assess tumour response, tailored to childhood and adolescent cancers, enabling an accurate evaluation of treatment outcomes, monitoring of long-term effects of treatment, and identification of potential risks such as second cancers, thereby improving overall patient care;
• Ultimately, provide scientific evidence to deliver affordable and accessible treatments for children and adolescents with cancer to be implemented by healthcare systems at the level of local communities, European regions, Member States and Associated Countries;
• All datasets produced should be described with metadata records in the EU dataset catalogue of the European Health Data Space, while all tools and models should take advantage of current European research infrastructures, should follow the principles of open science and made available through the future UNCAN.eu platform[[https://healthdcat-ap.github.io/]].

The topic is designed to fill a gap in terms of knowledge, expertise, tools, data and resources in paediatric oncology, to be achieved through multinational, cross-sectoral and multidisciplinary cooperation.

For that purpose, projects should bring together a diverse range of stakeholders and organizations from across Europe and beyond, including academia, data scientists, paediatric oncology centers, hospitals, healthcare practitioners, liquid biopsy companion diagnostics experts, cancer patients and survivors, caregivers, patients and survivors organisations, regulators, and industry etc., to foster collaboration and accelerate the development of innovative cancer treatments and therapeutic approaches including companion diagnostics. Timely contact with regulatory authorities should be foreseen to inform the trial design and feasibility. Use of artificial intelligence tools is encouraged, whenever relevant. Existing resources such as paediatric cancer registries should be appropriately exploited.

This topic requires the effective contribution of Social Science and Humanities (SSH) disciplines and the involvement of SSH experts, institutions as well as the inclusion of relevant SSH expertise in the successful proposal, to produce meaningful and significant effects enhancing the societal impact of the related research activities.

Successful proposals are expected to build on the support of the Knowledge Centre on Cancer (KCC)[[Hosted by the European Commission's Joint Research Centre (JRC). Especially through the ’European Guidelines and Quality Assurance Schemes for Breast, Colorectal and Cervical Cancer Screening and Diagnosis‘, and the ’European Cancer Information System (ECIS)’ and the ’European Cancer Inequalities Registry (ECIR), see https://knowledge4policy.ec.europa.eu/cancer_en]] to foster EU alignment and coordination. Due consideration should be given to existing EU-funded initiatives (and if relevant other initiatives), including PedCRIN/ECRIN[[PedCRIN | Ecrin]] relevant initiatives supported by the Innovative Health Initiative, such as ITCC4[[ITCC-P4 GmbH Paediatric Preclinical Proof of Concept Platform (itccp4.com)]], c4c[[conect4children is a pan-European clinical trial network]], EU PEARL[[https://eu-pearl.eu/]] or the European Reference Network for Paediatric Oncology, ERN PaedCan[[Home - ERN PaedCan (ern-net.eu)]]

The Commission will facilitate coordination. Proposals should include a budget for networking, attendance at meetings, and potential joint activities[[Examples of these activities are research or research capacity, organising joint workshops, establishing best practices, joint communication or citizen engagement activities with projects funded under other clusters and pillars of Horizon Europe, or other EU programmes, as appropriate. Proposals are not required to include details of these activities, as they will be defined during the grant agreement preparation phase and during the life of the project.]] and will be asked to join the 'Diagnosis and Treatment' cluster for the Cancer Mission[[In order to address the objectives of the Cancer Mission, participants will collaborate in project clusters to leverage EU-funding, increase networking across sectors and disciplines, and establish a portfolio of Cancer Mission R&I and policy actions.]]

Applicants should provide details of the clinical studies in the dedicated annex using the template provided in the submission system.