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.