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

NCT ID: NCT05906407

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-19
• Study Completion Date: 2028-12-31

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

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).

Conditions

Early-Stage Breast Cancer; Neoadjuvant Therapy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Genomic Profiling / Sequencing

Procedure: genomic profiling (Whole-Genome- / Exome-Sequencing + RNA-Sequencing) in high-risk early breast cancer patients pre- and post neoadjuvant therapy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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
• Study entry is possible for patients with primary eBC at three timepoints:

• 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
• Option C: eBC patients after surgery and planned or conducting standard-of-care (SoC) post-neoadjuvant chemotherapy can be enrolled after surgery until the last cycle of standard post-neoadjuvant chemotherapy, if they fulfill the following criteria

• HER2+ BC or TNBC: non-pCR
• HR+/HER2- BC: non-pCR and CPS-EG score ≥ 3 or non-pCR, ypN+ and CPS-EG-score ≥ 2 Note: Option C is not the preferred entry time-point Note: in case of loco-regional relapse, neoadjuvant treatment is not mandatory
• Patients must be willing to donate a recent tumour sample to the registry Note: fresh tumour tissue is preferred
• Patients, who agreed to and were able to sign the informed consent form (ICF).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

German Cancer Research Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Lichter, PhD

Role: PRINCIPAL_INVESTIGATOR

German Cancer Research Center (DKFZ) Heidelberg

Andreas Schneeweiss, MD

Role: PRINCIPAL_INVESTIGATOR

National Center for Tumor Diseases, Heidelberg

Verena Thewes, PhD

Role: PRINCIPAL_INVESTIGATOR

National Center for Tumor Diseases, Heidelberg

Locations

University Hospital Augsburg

Augsburg, , Germany

Site Status: RECRUITING

Charité - Berlin

Berlin, , Germany

Site Status: RECRUITING

University Hospital Köln

Cologne, , Germany

Site Status: NOT_YET_RECRUITING

Medical Faculty and University Hospital Carl Gustav Carus

Dresden, , Germany

Site Status: RECRUITING

University Hospital Erlangen

Erlangen, , Germany

Site Status: RECRUITING

University Hospital Essen

Essen, , Germany

Site Status: NOT_YET_RECRUITING

National Center for Tumor Diseases (NCT) Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Caritas Hospital St. Josef

Regensburg, , Germany

Site Status: RECRUITING

Robert Bosch Hospital Stuttgart

Stuttgart, , Germany

Site Status: RECRUITING

University Hospital Tübingen

Tübingen, , Germany

Site Status: RECRUITING

University Hospital Ulm

Ulm, , Germany

Site Status: RECRUITING

University Hospital Würzburg

Würzburg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Andreas Schneeweiss, MD

Role: CONTACT

Andreas.Schneeweiss@med.uni-heidelberg.de

0049-6221-5636051

Peter Lichter, PhD

Role: CONTACT

Peter.Lichter@Dkfz-Heidelberg.de

0049-6221-424619

Facility Contacts

Nina Ditsch, MD

Role: primary

Jens-Uwe Blohmer, MD

Role: primary

Pauline Wimberger, MD

Role: primary

Peter Fasching, MD

Role: primary

Andreas Schneeweiss, MD

Role: primary

andreas.schneeweiss@med.uni-heidelberg.de

0049-6221-5636051

Peter Lichter, PhD

Role: backup

Peter.Lichter@DKFZ.de

0049-6221-424619

Stephan Seitz, MD

Role: primary

Matthias Schwab, MD

Role: primary

Andreas Hartkopf, MD

Role: primary

Wolfgang Janni, MD

Role: primary

Achim Wöckel, MD

Role: primary

Jessica Salmen, MD

Role: backup

Other Identifiers

01EK2202A

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

S-790/2018

Identifier Type: -

Identifier Source: org_study_id