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

NCT05906407 | Recruiting

• 2 other identifiers: S-790/201801EK2202A
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 12

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.

Conditions

Early-Stage Breast Cancer; Neoadjuvant Therapy

Keywords

Early Breast Cancer; Precision Oncology; Personalized Oncology; Genomic Profiling; Genomics-Guided Biomarker-Stratification; Postneoadjuvant-Therapy

Outcome Measures

Primary Outcomes (3)

• 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.

  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).

  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.

  31/12/2028

Secondary Outcomes (5)

• Identification and characterization of prognostic and predictive biomarkers, drug targets, resistance mechanisms and the immune environment.

  31/12/2028

• Monitoring of treatment response and elucidation of resistance mechanisms using liquid biopsies.

  31/12/2028

• Ex vivo cultivation of patient-derived biomaterial for research purposes.

  31/12/2028

• Delineation of tumour-microenvironment interactions with the immune systems.

  31/12/2028

• Characterization of genetic alterations affecting drug metabolism (pharmacogenomics).

  31/12/2028

Interventions

Genomic Profiling / Sequencing OTHER

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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).

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• German Cancer Research Center: lead
• University Hospital Heidelberg: collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (12)

University Hospital Augsburg

Augsburg, Germany

RECRUITING

Charité - Berlin

Berlin, Germany

RECRUITING

University Hospital Köln

Cologne, Germany

NOT YET RECRUITING

Medical Faculty and University Hospital Carl Gustav Carus

Dresden, Germany

RECRUITING

University Hospital Erlangen

Erlangen, Germany

RECRUITING

University Hospital Essen

Essen, Germany

NOT YET RECRUITING

National Center for Tumor Diseases (NCT) Heidelberg

Heidelberg, Germany

RECRUITING

Caritas Hospital St. Josef

Regensburg, Germany

RECRUITING

Robert Bosch Hospital Stuttgart

Stuttgart, Germany

RECRUITING

University Hospital Tübingen

Tübingen, Germany

RECRUITING

University Hospital Ulm

Ulm, Germany

RECRUITING

University Hospital Würzburg

Würzburg, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Fresh-frozen tissue and EDTA-blood

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Genetic Profile; Base Sequence

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Genetic Background; Genetic Phenomena; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas Schneeweiss, MD

CONTACT

0049-6221-5636051; Andreas.Schneeweiss@med.uni-heidelberg.de

Peter Lichter, PhD

CONTACT

0049-6221-424619; Peter.Lichter@Dkfz-Heidelberg.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: June 15, 2023
• Study Start: April 19, 2019
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 19, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12)