German Clinical Trials Register

Acronym/abbreviation of the study

INFORM

URL of the study

http://www.dkfz.de/de/inform/index.html

Brief summary in lay language

INFORM REGISTRY STUDY: Although current treatment of childhood malignancies results in overall cure rates in the order of 75% with modern multi-modal protocols, relapse from high risk disease remains a tremendous clinical problem. The concept of the INFORM registry is to biologically characterize tumor samples collected through routine standard of care biopsies for all pediatric patients with relapsed or refractory high risk diseases for whom no further standard of care therapy is available. With the help of state-of-the-art moleculargenetic technologies each individual tumor is charactarized. An expert panel classifies the found targets according to clinical relevance.No therapy recommendation will be given within this registry study. The treating physician has access to the molecular information/targets of the patient and can use these data for therapy decision-making.

Brief summary in scientific language

Although current treatment of childhood malignancies results in overall cure rates in the order of 75% with modern multi-modal treatment protocols, relapses from high risk disease remains a tremendous clinical problem. Only a small proportion of patients with relapses (about 10%) can be cured. This medical need will be addressed with the INFORM project „INdividualized Therapy FOr Relapsed Malignancies in Childhood“. The INFORM consortium constitutes leading pediatric oncologists of study groups of the Society for Pediatric Oncology und Hematology (GPOH) and renowned scientists in the field of high content genomics research. 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 high risk disease for which no further standard of care therapy is available, independently of histological diagnosis. State-of-the art next-generation sequencing technologies will be applied to get a “fingerprint” of each individual tumor. An expert panel of experienced pediatric oncologists, bioinformaticians, biologists and pharmacologists classifies and weighs the aberrations/targets found for each single patient according to clinical relevance. These molecular targets shall be available in less than 4 weeks after sample receipt and will be entered in the central database. No therapy recommendation will be given within this registry study. The treating physician has access to the molecular information/targets of their patients and carries the full responsibility as to whether and in which way they use these data for therapy decision making. The intention of the INFORM Registry is to establish the technical, structural and information basis for a future clinical trial (AMG) for personalized pediatric oncology. The primary objectives of the INFORM Registry are: To establish the logistics (tissue sample submission, analysis and classification), to establish an individualized risk management support (working group with experts in drug interaction) and access modes for targeted compounds and to establish a database for the documentation of the sequencing results, of identified clinically relevant targets, of clinical courses, and of therapies, including single experimental treatments (Einzelheilversuche). Secondary objectives of the INFORM Registry are the descriptive and exploratory analyses of registered patients regarding response rates, progression free and overall survival. In addition to meanwhile established INFORM analyses [8], a standardized high-throughput drug sensitivity screening platform will be set up to directly test efficacy of drugs on viable tumor cells of the individual patient. Sensitivity and resistance profiles will be further validated in vitro and in vivo in patient derived tumor model systems. Results of screening data will be integrated with obtained Next Generation Sequencing (NGS) data derived from the same tumor and will be made available during target decision board discussions. These analyses require availability of fresh native tumor tissue that is submitted in a timely manner. Through prospective collection and analyses of liquid biopsy specimens, plasma and cerebrospinal fluid (for brain tumors only), the project will address the question whether tumor derived circulating genetic information is suitable for molecular diagnostics and/or target identification. Within a research program of the DKTK network (proteomic platform) additional protein profiles (proteomics) will be generated for selected samples. Results will be integrated with sequencing data from standard INFORM pipelines to address the question whether proteomic information may serve as an informative additional layer of information to guide personalized patient treatment in the future. Inclusion criteria for the registry population are relapsed/progressive or refractory diagnoses of ALL-HR, ALL Post-SCT, AML, rhabdoid tumor, ependymoma, medulloblastoma, ewing-sarcoma, high grade glioma, high risk neuroblastoma, non-hodgkin lymphoma, osteosarcoma, soft tissue sarcoma. Patients with primary diagnosis high-grade glioma (incl. DIPG), primary diagnosis soft tissue sarcoma or ETMR, for which no curative treatment is established, may also be enrolled. Exceptionally, “other” pediatric refractory or progressive/relapsed entities including rare tumor diseases may be registered following consultation with the INFORM trial office (and in case of rare tumor diseases with the GPOH STEP registry, in case of nephroblastoma, hepatoblastoma, retinoblastoma, malignant endocrine tumor, germ cell tumor or ETMR with the GPOH relevant study group) before enrollment. The patients are 0 to 40 years old and were treated according to a protocol of the GPOH or an equivalent protocol as their first-line protocol. Although patients can be included up until the age of 40 years, they must have had their primary diagnosis below the age of 21 years. The collection of tumor and blood samples as well as cerebrospinal fluid (for brain tumors only) is carried out as part of routine standard of care of the patients. About 150 patients per year in Germany plus additional international patients shall be included. Patients can be enrolled from GPOH centers in Germany and international partners of the INFORM consortium.