Early-Stage Breast CancerCOGNITIONNCT05906407
COGNITION: Genomics-Guided Precision Oncology in Early High-Risk Breast Cancer
An observational study of Early-Stage Breast Cancer and Neoadjuvant Therapy, run by German Cancer Research Center at 12 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Early-Stage Breast Cancer, Neoadjuvant Therapy
- What is being tested?
- Genomic Profiling / Sequencing
- How many people
- 2,000 participants
- Where
- 12 sitesGermany
- Study dates
- 19 Apr 2019to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study 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).
Who may be able to join
- 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
Show all 10Show fewer
- 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).
Who cannot join
- 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 locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Germany12 sites, 12 recruiting
- Recruiting
University Hospital Augsburg
Augsburg
Nina Ditsch, MD
- Recruiting
Charité - Berlin
Berlin
Jens-Uwe Blohmer, MD
- Recruiting
University Hospital Köln
Cologne
Christian Maurer, MD
- Recruiting
Medical Faculty and University Hospital Carl Gustav Carus
Dresden
Pauline Wimberger, MD
- Recruiting
University Hospital Erlangen
Erlangen
Peter Fasching, MD
- Not yet recruiting
University Hospital Essen
Essen
- Recruiting
National Center for Tumor Diseases (NCT) Heidelberg
Heidelberg
Andreas Schneeweiss, MD, 0049-6221-5636051, andreas.schneeweiss@med.uni-heidelberg.de
Peter Lichter, PhD, 0049-6221-424619, Peter.Lichter@DKFZ.de
- Recruiting
Caritas Hospital St. Josef
Regensburg
Stephan Seitz, MD
- Recruiting
Robert Bosch Hospital Stuttgart
Stuttgart
Matthias Schwab, MD
- Recruiting
University Hospital Tübingen
Tübingen
Andreas Hartkopf, MD
- Recruiting
University Hospital Ulm
Ulm
Wolfgang Janni, MD
- Recruiting
University Hospital Würzburg
Würzburg
Achim Wöckel, MD
Jessica Salmen, MD
About this study
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)
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.
Read more
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.
Read the 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
- Being tested
- Genomic Profiling / Sequencing
- Keywords
- Early Breast Cancer, Precision Oncology, Personalized Oncology, Genomic Profiling, Genomics-Guided Biomarker-Stratification, Postneoadjuvant-Therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genomic Profiling / SequencingOther
Procedure: genomic profiling (Whole-Genome- / Exome-Sequencing + RNA-Sequencing) in high-risk early breast cancer patients pre- and post neoadjuvant therapy
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 31/12/2028
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).
Measured: 31/12/2028
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.
Measured: 31/12/2028
Secondary outcomes (5)
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.
Measured: 31/12/2028
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.
Measured: 31/12/2028
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).
Measured: 31/12/2028
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.
Measured: 31/12/2028
Characterization of genetic alterations affecting drug metabolism (pharmacogenomics).
- Assessment of the technical validation rate of somatic and germline alterations or further alterations in specific pathways by independent methods.
Measured: 31/12/2028
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start19 Apr 2019
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-Stage Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Cancer Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Heidelberg, German Federal Ministry of Education and Research
- Responsible party
- Sponsor
- Investigators
- Peter Lichter, PhD, Principal investigator, German Cancer Research Center (DKFZ) HeidelbergAndreas Schneeweiss, MD, Principal investigator, National Center for Tumor Diseases, HeidelbergVerena Thewes, PhD, Principal investigator, National Center for Tumor Diseases, Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05906407
- Sponsor's protocol ID
- S-790/2018
- Other IDs
- 01EK2202A
- Acronym
- COGNITION
- Status last verified
- Jun 2026
- First submitted
- 8 Dec 2022
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05906407
- Acronym / sponsor ID
- COGNITION / S-790/2018
- Conditions
- Early-Stage Breast Cancer, Neoadjuvant Therapy
- Keywords
- Early Breast Cancer, Precision Oncology, Personalized Oncology, Genomic Profiling, Genomics-Guided Biomarker-Stratification, Postneoadjuvant-Therapy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- German Cancer Research CenterUniversity, hospital or other
- Collaborators
- University Hospital Heidelberg, German Federal Ministry of Education and Research
- Study start
- 19 Apr 2019 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study 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).
Key inclusion criteria (10 listed)
- 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:
- 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).
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genomic Profiling / SequencingProcedure: genomic profiling (Whole-Genome- / Exome-Sequencing + RNA-Sequencing) in high-risk early breast cancer patients pre- and post neoadjuvant therapy | Other | – |
Primary outcome
Comprehensive assessment of clinical patient data, collection of biomaterial and implementation of genomics- / molecular- and immune- guided precision medicine in eBC into the clinics.
Time frame: 31/12/2028
• 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.
Setting up a clinical and multidimensional, molecular diagnostic registry platform for patients with eBC and high risk for relapse.
Time frame: 31/12/2028
• 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).
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).
Time frame: 31/12/2028
• Total number/percentage of patients enrolled in subsequent interventional trials.
5 secondary outcomes
Identification and characterization of prognostic and predictive biomarkers, drug targets, resistance mechanisms and the immune environment.
Time frame: 31/12/2028
Monitoring of treatment response and elucidation of resistance mechanisms using liquid biopsies.
Time frame: 31/12/2028
Ex vivo cultivation of patient-derived biomaterial for research purposes.
Time frame: 31/12/2028
Delineation of tumour-microenvironment interactions with the immune systems.
Time frame: 31/12/2028
Characterization of genetic alterations affecting drug metabolism (pharmacogenomics).
Time frame: 31/12/2028
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peter Lichter, PhD principal investigator
German Cancer Research Center (DKFZ) Heidelberg
Andreas Schneeweiss, MD principal investigator
National Center for Tumor Diseases, Heidelberg
Verena Thewes, PhD principal investigator
National Center for Tumor Diseases, Heidelberg
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Early-Stage Breast Cancer and Neoadjuvant Therapy, run by German Cancer Research Center at 12 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andreas Schneeweiss, MD (0049-6221-5636051, Andreas.Schneeweiss@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comprehensive assessment of clinical patient data, collection of biomaterial and implementation of genomics- / molecular- and immune- guided precision medicine in eBC into the clinics. (time frame: 31/12/2028). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.