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JOURNAL ONKOLOGIE – STUDIE
COGNITION

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

Rekrutierend

NCT-Nummer:
NCT05906407

Studienbeginn:
April 2019

Letztes Update:
15.11.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Breast Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
German Cancer Research Center

Collaborator:
University Hospital Heidelberg, German Federal Ministry of Education and Research,

Studienleiter

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

Kontakt

Andreas Schneeweiss, MD
Kontakt:
Phone: 0049-6221-5636051
E-Mail: Andreas.Schneeweiss@med.uni-heidelberg.de» Kontaktdaten anzeigen

Studienlocations
(3 von 5)

National Center for Tumor Diseases (NCT) Heidelberg
Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Andreas Schneeweiss, MD
Phone: 0049-6221-5636051
E-Mail: andreas.schneeweiss@med.uni-heidelberg.de

Peter Lichter, PhD
Phone: 0049-6221-424619
E-Mail: Peter.Lichter@DKFZ.de» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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. (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.

2. 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).

3. 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.

Secondary outcome:

1. Identification and characterization of prognostic and predictive biomarkers, drug targets, resistance mechanisms and the immune environment. (Time Frame - 31/12/2028):
• 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.

2. Monitoring of treatment response and elucidation of resistance mechanisms using liquid biopsies. (Time Frame - 31/12/2028):
• Association between the detection of circulating tumour cells (CTCs), circulating tumour DNA (ctDNA) and outcome measured as OS, IDFS and DDFS.

3. Ex vivo cultivation of patient-derived biomaterial for research purposes. (Time Frame - 31/12/2028):
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).

4. Delineation of tumour-microenvironment interactions with the immune systems. (Time Frame - 31/12/2028):
• 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.

5. Characterization of genetic alterations affecting drug metabolism (pharmacogenomics). (Time Frame - 31/12/2028):
• Assessment of the technical validation rate of somatic and germline alterations or further alterations in specific pathways by independent methods.

Geprüfte Regime

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

Quelle: ClinicalTrials.gov


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