INFORM – About the project

Aims

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 sequencing results, identified clinically relevant targets, clinical courses, and therapies / 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, 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. 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. 

 

Clinical studies

The INFORM register provides a solid database for the development of clinical studies. For example, we examine the frequency of mutations for which “intelligent” drugs are available. Together with independent experts, we select the molecular changes for which one or two of these drugs are best suited. In future clinical studies, it will then be examined whether, regardless of the type of cancer, individualized therapy achieves better results than standard chemotherapy for patients with these molecular changes.

 

Why children?

Of course, we hope first and foremost to be able to improve the survival chances of the young patients. This is made easier by the fact that pediatric oncologists throughout Germany, but also internationally, have always worked closely together. This is the only way to make such a comprehensive study possible, in which more than fifty centers in Germany alone are working together to treat the children. We also now know that childhood tumors have about a hundred times fewer mutations than most adult cancers. This makes the task of identifying the tumor-causing mutations and combining them with the “right” intelligent drug much easier. The experience we gain in the course of the INFORM study will be of great benefit in planning similar studies in adult cancer patients.