The study objectives are:
- Does the slope of decrease of the plasma tumor DNA predict PFS and/or OS? (investigation of deepness of response)
Besides standard clinical definition, novel biomarkers are needed to biologically define an oligometastatic disease status in the future and to better assess response and the occurrence of resistance during treatment.
Clonal selection pressure has gained increasing interest in various tumor entities and with emerging targeted treatment options. In colorectal cancer, tumor RAS mutation status represents a validated predictive biomarker for the efficacy of EGFR-antibody treatment. However, in a RAS wt population treated with EGFR inhibition, owing to inherent genetic tumor heterogeneity, clonal selection pressure can result in the occurrence of resistance mediated by RAS mutated clones during targeted treatment. Interestingly, these resistant clones can be found by highly sensitive testing within the initial tumor lesions at very low frequency. Recently, different highly sensitive methods have been developed to monitor DNA mutations within the circulating free tumor DNA from blood samples and the term "liquid biopsies” has been coined.
Additionally, miRNA expression profiles from tumor samples have been described that might be useful to characterize an oligometastatic disease status. However, further validation of this concept within clinical trials is needed.
In principle, this pilot study is intended to generate data enabling the design of a larger consecutive (probably randomized) study format. Data of the pilot will be compared with data from the "PlaCol” patient cohort sampled in Paris Université Descartes (PI: Prof. Pierre Laurent-Puig). Second, our intention is to develop a protocol for public funding either as a randomized study or a free plasma DNA alteration-tailored treatment approach.
Pilot study: single-arm, biomarker-driven study to explore the evolution of genetic alterations during treatment of oligometastatic disease
Leipziger Str. 44
Tel.:+49 391 6713030