Comprehensive Assessment of Clinical Features and Biomarkers to Identify Patients With Advanced or Metastatic Breast Cancer for Marker Driven Trials in Humans (CATCH)

简要总结

详细描述

Study Flow CATCH has the goal to implement personalized oncology workflows into the clinic. The clinical precision oncology core backbone encompasses a streamlined diagnostic end-to-end pipeline: Patient screening and enrolment: Metastatic breast cancer (mBC) patients at initial diagnosis of locally-advanced-/ distant metastasis and any other clinical progress are screened for eligibility. The treating physician has to obtain written informed consent prior to enrolment. Collection of biomaterial: Fresh-frozen tumor tissue from progressive prognostic-relevant metastatic lesions is collected during standard-of-care routine procedures at study entry. Consecutive biopsies can be offered at progress. Blood samples are taken at baseline (V1) to account for germline controls and can be sequentially repeated at 3-monthly intervals for monitoring of therapy response. Processing and analyses of patient samples: Biomaterials are centrally processed (standard histology/IHC and pathology review for tumor content; analyte extraction, QC according to standardized, quality-controlled, accredited workflows (DIN EN ISO/IEC 17025). Analyte extraction on fresh-frozen tissue encompasses DNA, RNA and protein isolation. Molecular profiling (Sequencing): Genomic profiling (DIN EN ISO/IEC 17025) is centrally processed to ensure standardization and encompasses whole-genome sequencing (WGS) on fresh-frozen tissue biopsies or whole-exome sequencing (WES) on FFPE specimens (in case of unsuccessful biopsy sampling on recent lesion due to low tumor cell content) complemented by RNA-sequencing. Clinical bioinformatics /Data curation: Tumor- and treatment-relevant genomic aberrations together with standard clinical as well as histopathological parameters are analyzed and put into the clinical context to delineate biomarkers and actionable alterations as well as to tackle the underlying biology of treatment-resistance. Molecular Tumor Board (MTB): Molecular data and conclusive biomarker profiles are discussed by clinicians, bioinformaticians, molecular biologists, human geneticists and pathologists in a weekly interdisciplinary MTB established at NCT Heidelberg. Treatment-relevant biomarkers and actionable drug targets are validated independently. Therapeutic options are prioritized within a molecular report. Therapy Implementation: Patients will be informed in detail by the treating physician to discuss potential genetically-tailored treatment options. The major goal is to offer patients further interventional clinical trials and drive assignment towards genomics-guided matched biomarker / drug combinations. Follow-up / Documentation Schedule: Clinical documentation is conducted by authorized study personal at study entry in a certified electronic case report form (eCRF) and subsequently every 3 months for at least 3 years, at any staging interval or cancer-specific therapy change to generate a comprehensive patient registry. To ascertain comprehensive follow-up, only patients will be enrolled who will be treated locally at the involved trial sites. Molecular data will be systematically collected to drive translational exploratory research projects. The following data are collected and stored (baseline and follow-up assessments) * patient identifier /demographics (including sex, age at diagnosis, family history) * cancer type / medical history / characteristics diagnosis (including date of diagnosis) * clinical outcome / longitudinal disease assessments: relapse and progression * genomic and transcriptomic data * ECOG status * sample information (e.g. specimen type, tumor histological type, anatomical location, tissue analyses) * health-related Quality-of-Life (QoL) / Patient-Reported Outcomes (PROs) Translational scientific companion programs: Excess biomaterial not needed for the diagnostic precision oncology approach can be used for exploratory research (e.g. ex vivo approaches, liquid biopsies, immunophenotyping). Results / Outcome Evaluation:Molecular data will be analysed and interpreted on complementary levels. Biomarkers and molecular aberrations such as mutations, amplifications and aberrant gene expression are evaluated for their tumor-relevance and clinical potential to assign patients for specific clinical trials with targeted treatment approaches.

主要结局

次要结局

• Secondary outcome measures Building novel therapeutic hypothesis.(31/12/2030)