The population for the INFORM Registry includes refractory/relapsed/progressive pediatric cases of ALL-HR, ALL Post-SCT, AML, rhabdoid tumor, ependymoma, medulloblastoma, ewing sarcoma, high grade glioma, neuroblastoma, non-hodgkin lymphoma, osteosarcoma, soft tissue sarcoma and “other” tumor diseases including rare tumors (STEP registry), nephroblastoma, hepatoblastoma, retinoblastoma, malignant endocrine tumours, germ cell tumors and “other”. Patients with primary diagnosis high-grade glioma (
Conditions
Interventions
Group 1: The concept of the INFORM-program is to biologically characterize tumor samples (collected through routine standard of care biopsies) for all pediatric patients with relapsed or refractory hi
Sponsors
Deutsches Krebsforschungszentrum / Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Age
No minimum to 40 Years
Inclusion criteria
Inclusion criteria: • Children, adolescents and young adults 0-40 years old with refractory/relapsed/progressive oncological disease following first, second or third line treatment protocols including targeted treatment approaches considering entity-specific high-risk criteria. High-grade gliomas (incl. DIPG), specific soft tissue sarcomas, ETMR and rare tumor diseases included in the STEP Registry, e.g. carcinoma, melanoma, rare gonadal tumors or in the MET Registry, e.g. ACC, ACx, PCC/PGL by SDHB or metastases, MTC, NETs except appendix may be enrolled upon primary diagnosis • Patients can be included up until the age of 40 years, but they must have had their primary diagnosis below the age of 21 years • No established curative treatment options • Life expectancy > 3 months and sufficient general condition (Lansky = 50 or Karnofsky = 50) • Patient treated in Germany or in one of the partner countries • First-line treatment within one of the therapy optimization/registry trials of the Society of Pediatric Oncology and Hematology (GPOH) or an equivalent protocol, except for primary diagnosis high-grade gliomas (incl. DIPG), specific primary soft tissue sarcomas, ETMR, rare tumor diseases included in the STEP Registry or malignant endocrine tumors included in the MET Registry. • Inclusion in INFORM Registry discussed with and agreed by respective GPOH entity study group (or the respective National Coordinator). • Histopathological/molecular confirmation of clinically suspected diagnosis (result/confirmation does not have to be available at the time of registration). • Routine surgery/puncture of the current oncological disease as part of standard of care treatment. • Time between surgery/puncture of the current oncological disease and receipt of all required samples and information in the INFORM Incoming / Sample Processing Laboratory at the CCU Neuropathology in Heidelberg = 8 weeks. • For German patients with solid tumors and brain tumors suitable fresh frozen tumor tissue of the current disease episode and non-malignant germline material available (to be sent to INFORM Registry for molecular analysis). For all international patients (and German patients with non-solid tumors) already extracted tumor DNA and tumor RNA from fresh frozen malignant material of the current disease episode as well as DNA from non-malignant germline material available (to be sent to INFORM Registry for molecular analysis). • Tumor cell content / tumor infiltration / blast content in submitted tumor material has to be at least 40% (in case of non-solid tumors at least 30%). • Written informed consent of patients and/or legal guardians.
Exclusion criteria
Exclusion criteria: AML: Acute promyelocytic leukemia. Acute myeloid leukemia in patients with Down Syndrome.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Continuous improvement of logistics for personalized treatment •Sample submission of fresh frozen tumor material and non-malignant material, molecular analysis and target identification within 4 weeks after receipt of all required samples and information in the INFORM Incoming / Sample Processing Laboratory at the CCU Neuropathology in Heidelberg •Collection of fresh vital tumor material for drug sensitivity profiling and establishment of in vivo and in vitro tumor models Establishment of a sustainable data integration platform to enable data sharing and partnership with academic researchers, industry partners, and regulators at an international level for molecular data and clinical data •Collecting and providing information about individual druggable targets •Collecting and providing information about targeted therapy options •Documentation of individualized treatments (Einzelheilversuche) and follow-up Collection of data on individual •Clinical development •Genomics •Epigenomics •Transcriptomics •Drug response profiles of fresh vital tumor material (standardized high-throughput screening platform) •Characteristics of high-risk refractory/relapsed/progressive pediatric malignancies •Liquid biopsies (circulating tumor DNA) •Proteomics/phospo-proteomics •Patient-derived short and long term culture and xenograft (PDX) models derived from fresh vital tumor samples Evaluation of collected data •Further development and evaluation of the target prioritization algorithm to identify and prioritize actionable target patterns across histological diagnoses •Documentation of the data from the standardized high-throughput drug sensitivity screening platform •Definition and refinement of complex predictive biomarkers (including retrospective analysis of data) •Definition of a set of “targeted compounds of interest” within the registry population •Documentation of a number of patients per year / per entity suitable for future AMG trials of personalized oncology in terms of | — |
Secondary
| Measure | Time frame |
|---|---|
| • Evaluation of response rates, PFS and OS of patients, overall and stratified for different (targeted) treatments, diagnoses and actionable target types. • Establishment of in vitro and in vivo tumor models from fresh vital tumor material for sharing with scientific partners, including companies and healthcare stakeholders at an international level • Comparison of drug response profiles of patient-derived short and long term cultures and xenograft (PDX) models with correlated clinical response profiles of the patients • Evaluation of liquid biopsies as tools for molecular diagnostics and target identification • Evaluation of transcriptomic and proteomic/phospo-proteomic analysis to identify potential actionable targets and pathways, and to predict potential positive effects of drugs | — |
Countries
Austria, Belgium, Czechia, Finland, Germany, Greece, Israel, Norway, Poland, Portugal, Slovenia, Sweden, Switzerland
Contacts
Public ContactCecilia Zuliani
KiTZ Clinical Trial Unit
Outcome results
None listed