COGNITION: Genomics-Guided Precision Oncology in Early High-Risk Breast Cancer

Sponsor

German Cancer Research Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05906407

Collaborator

University Hospital Heidelberg (Other), German Federal Ministry of Education and Research (Other)

2,000

Enrollment

Locations

116.4

Anticipated Duration (Months)

400

Patients Per Site

3.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

to couple the observational, diagnostic registry platform to the independent, biomarker-stratified clinical therapy trial COGNITION-GUIDE.

Condition or Disease	Intervention/Treatment	Phase
Early-Stage Breast Cancer Neoadjuvant Therapy	Other: Genomic Profiling / Sequencing

Detailed Description

Patient registration and enrolment: pts with histologically confirmed early breast cancer and indication for neoadjuvant chemotherapy (NACT, any subtype) who give their consent for the integrative genomic profiling study as pre-requisite for molecular stratification in the coupled phase II COGNITION-GUIDE (NCT05332561) therapy trial.
Collection of biomaterial: Fresh-frozen tumor tissue from primary breast tumors is collected during routine procedures at study entry (T1: baseline-treatment naive) and from residual bulk tumors (T2: w/o pCR after NACT). To account for germline alterations (genomic control) and to fuel companion programs, consecutive blood samples are taken at baseline (V1) and after NACT (V2).
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. Molecular profiling & clinical bioinformatics: Genomic profiling encompasses Whole-Genome on fresh-frozen tissue biopsies or Whole-Exome on FFPE surgical specimens (if fresh-frozen tissue has insufficient tumor cell content >20%). Both options are complemented by RNA-Seq facilitating an unbiased integrated view on the expression of multiple biomarkers.
Clinical curation and data interpretation: Based on the curative intent, a rigorous, pre-defined biomarker algorithm (strong and soft biomarkers) is applied. This strategy allows assessment whether the tumor profile qualifies for one of the molecular-guided treatment arms.
Molecular Tumor Board (MTB): Molecular data are interpreted by clinicians, bioinformaticians, molecular biologists, human geneticists and pathologists in a weekly interdisciplinary MTB established at NCT. Treatment-relevant biomarkers and actionable drug targets are validated independently. Disease-relevant germline alterations will lead to genetic counselling.
Treatment recommendations and therapy implementation: Conclusive biomarker profiles from clinical, histopathological and genomic data drive assignment to one treatment arm. Therapeutic options are prioritized within a molecular report.
Patient Monitoring / Follow-Up: Comprehensive documentation will be conducted at study entry and every 6 mths for 10 years.
Pre-Clinical Companion Programs: The valuable pre- and post neoadjuvant biomaterial will be exploited to fuel collaborative studies around therapy failure, biomarker development and tracking of residual cancer burden in liquid biopsies (ctDNA).

Study Design

Study Type:

Observational

Anticipated Enrollment :

2000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

COGNITION: Comprehensive Assessment of Clinical Features, Genomics and Further Molecular Markers to Identify Patients With Early Breast Cancer for Enrolment on Marker Driven Trials (Molecular Diagnostic Platform)

Actual Study Start Date :

Apr 19, 2019

Anticipated Primary Completion Date :

Dec 31, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Outcome Measures

Primary Outcome Measures

Assessment of feasibility and retrieval of the logistical, clinical and information basis to include patients into independent molecular-driven AMG trials (independent of this registry). [31/12/2028]
• Total number/percentage of patients enrolled in subsequent interventional clinical therapy trials
Setting up a clinical and multidimensional, molecular diagnostic platform for patients with early breast cancer at high risk of relapse to assess patient characteristics/ clinical patient data and molecular tumour features. [31/12/2028]
Total number/percentage of patients with early breast cancer and high risk for relapse i) eligible for genomic profiling, ii) successfully genomically-profiled tumours, iii) with conclusive biomarker profiles Clinical outcome of patients with early breast cancer (in terms of overall survival, invasive disease-free survival, distant relapse-free interval)

Secondary Outcome Measures

Identification and characterization of prognostic and predictive biomarkers and possible drug targets [31/12/2028]
• Association between specific biomarkers and response to treatment (outside of this registry) for early breast cancer patients measured as overall survival, invasive disease-free survival and distant relapse-free interval
Ex-vivo cultivation of patient-derived tumour and blood material. [31/12/2028]
• Descriptive characterization of tumour heterogeneity, tumour-microenvironment interactions and drug response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with histologically confirmed primary early potentially curative breast cancer (clinical stage I-III, irrespective of TNM or subtypes) assigned to receive neoadjuvant chemotherapy.
Patients must complete pre-operative neoadjuvant standard therapy.
Previous contralateral breast cancer is allowable unless it is considered "active" defined as a current need for cancer therapy.

Exclusion Criteria:

Advanced stage / metastatic (stage IV) breast cancer.
Inability to acquire tissue by biopsy or during surgery.

Contacts and Locations

Locations

	Site	City	Country
1	Charité - Berlin	Berlin	Germany
2	Medical Faculty and University Hospital Carl Gustav Carus	Dresden	Germany
3	University Hospital Erlangen	Erlangen	Germany
4	National Center for Tumor Diseases (NCT) Heidelberg	Heidelberg	Germany
5	University Hospital Ulm	Ulm	Germany

Sponsors and Collaborators

German Cancer Research Center
University Hospital Heidelberg
German Federal Ministry of Education and Research

Investigators

Principal Investigator: Peter Lichter, PhD, German Cancer Research Center (DKFZ) Heidelberg
Principal Investigator: Andreas Schneeweiss, MD, National Center for Tumor Diseases, Heidelberg
Principal Investigator: Verena Thewes, PhD, National Center for Tumor Diseases, Heidelberg