COGNITION: Genomics-Guided Precision Oncology in Early High-Risk Breast Cancer
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-80
SponsorGerman Cancer Research Center
About this trial
The COGNITION diagnostic platform elucidates the biomarker profile of neoadjuvant chemotherapy-resistant residual bulk tumors in high risk early breast cancer patients. The major goal is to provide a framework for genomic profiling, which serves as infrastructure for systematic biomarker-screening and -stratification for concise therapy-arm allocation in the interventional clinical phase II trial COGNITION-GUIDE (NCT05332561).
In patients, who display a poor response to standard-of-care neoadjuvant chemotherapy, tissue samples before and after neoadjuvant therapy are subjected together with blood samples to comprehensive genomic profiling to identify patients potentially benefiting from biomarker-guided interventions in COGNITION-GUIDE.
Samples not required for standard-of-care clinical procedures or genomic profiling are systematically collected in a dedicated bio-repository to fuel translational scientific companion programs. The continuously growing comprehensive database serves as an integrative resource for systematic, prospective multidimensional data collection (clinical records, biomaterial, genomic data).
In summary, the overarching goal is to generate a precision oncology platform i) to identify clinically-actionable biomarkers and drug targets that drive genomics-guided therapies and ii) to couple the observational, diagnostic registry platform to the independent, biomarker-stratified clinical therapy trial COGNITION-GUIDE.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female and male breast cancer patients aged ≥18 years.
Patients with primary early breast cancer (irrespective of subtypes) or - as an exception - patients with isolated loco-regional relapses that can be treated with a curative intention
Option A: patients planned to receive neoadjuvant chemotherapy are enrolled before starting the neoadjuvant treatment
Option B: patients with clinical non-complete response can be enrolled after the last cycle of neoadjuvant chemotherapy before surgery Note: Option A/B are strongly preferred entry time-points
Disqualifiers
Patients who did not sign or withdrew the informed consent form (ICF).
Inability to retrieve tissue for molecular profiling Any physical or mental handicap or severe comorbidities that would hamper the adequate cooperation with the patient.
Trial population
High-risk early-stage breast cancer (eBC) with suspected (non-clinical Complete Response - non-cCR ) and/or proven (non-pathological Complete Response - non-pCR) poor response towards NACT (irrespective of subtype).
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Genomic Profiling / Sequencing
Other interventionProcedure: genomic profiling (Whole-Genome- / Exome-Sequencing + RNA-Sequencing) in high-risk early breast cancer patients pre- and post neoadjuvant therapy
Treatment groups
No treatment groups listed
Trial outcomes
Primary outcomes
1
Comprehensive assessment of clinical patient data, collection of biomaterial and implementation of genomics- / molecular- and immune- guided precision medicine in eBC into the clinics.
• Total number/percentage of patients with eBC and high risk for relapse i) eligible for genomic profiling, ii) successfully genomically-profiled tumours, iii) with conclusive biomarker profiles.
Time frame
31/12/20282
Setting up a clinical and multidimensional, molecular diagnostic registry platform for patients with eBC and high risk for relapse.
• To record, show and benchmark the reality of high-throughput genomics-based medical care provided to patients with eBC and general outcome of patients (in terms of overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS).
Time frame
31/12/20283
Assessment of feasibility and retrieval of the logistical, clinical and information basis to screen and enroll patients for independent molecular-driven intervention trials (independent of this registry, e.g. COGNITION-GUIDE).
• Total number/percentage of patients enrolled in subsequent interventional trials.
Time frame
31/12/2028Secondary outcomes
1
Identification and characterization of prognostic and predictive biomarkers, drug targets, resistance mechanisms and the immune environment.
• Generation of catalogues of molecular aberrations, prognostic and predictive biomarkers and association between specific biomarkers and response to standard-of care treatment and/or targeted treatment for eBC (outside COGNITION) measured as OS, IDFS and DDFS.
Time frame
31/12/20282
Monitoring of treatment response and elucidation of resistance mechanisms using liquid biopsies.
• Association between the detection of circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and outcome measured as OS, IDFS and DDFS.
Time frame
31/12/20283
Ex vivo cultivation of patient-derived biomaterial for research purposes.
* Evaluation of the suitability of ex vivo model systems and liquid biopsy approaches (e.g. CTCs, ctDNA) to capture tumour heterogeneity, tumour-microenvironment interactions and drug response. * Characterization and modeling of the immune-compartment in tumour specimens and ex vivo culture approaches (immunoprofiling).
Time frame
31/12/20284
Delineation of tumour-microenvironment interactions with the immune systems.
• Descriptive assessment of the impact of germline alterations on drug-response and toxicity (pharmacogenomics) by generation of a comprehensive catalogue of alterations in conjunction with administered therapies and toxicities.
Time frame
31/12/2028Sponsors and contacts
Click on the lead sponsor to view all of their trials.
German Cancer Research Center
Lead sponsor
University Hospital Heidelberg
Collaborator
German Federal Ministry of Education and Research
Collaborator
Source ClinicalTrials.gov