Trial Title:
COGNITION: Genomics-Guided Precision Oncology in Early High-Risk Breast Cancer
NCT ID:
NCT05906407
Condition:
Early-Stage Breast Cancer
Neoadjuvant Therapy
Conditions: Official terms:
Breast Neoplasms
Conditions: Keywords:
Early Breast Cancer
Precision Oncology
Personalized Oncology
Genomic Profiling
Genomics-Guided Biomarker-Stratification
Postneoadjuvant-Therapy
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Other
Intervention name:
Genomic Profiling / Sequencing
Description:
Procedure: genomic profiling (Whole-Genome- / Exome-Sequencing + RNA-Sequencing) in
high-risk early breast cancer patients pre- and post neoadjuvant therapy
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).
Criteria for eligibility:
Study pop:
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).
Sampling method:
Non-Probability Sample
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Charité - Berlin
Address:
City:
Berlin
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Jens-Uwe Blohmer, MD
Facility:
Name:
Medical Faculty and University Hospital Carl Gustav Carus
Address:
City:
Dresden
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Pauline Wimberger, MD
Facility:
Name:
University Hospital Erlangen
Address:
City:
Erlangen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Peter Fasching, MD
Facility:
Name:
National Center for Tumor Diseases (NCT) Heidelberg
Address:
City:
Heidelberg
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Andreas Schneeweiss, MD
Phone:
0049-6221-5636051
Email:
andreas.schneeweiss@med.uni-heidelberg.de
Contact backup:
Last name:
Peter Lichter, PhD
Phone:
0049-6221-424619
Email:
Peter.Lichter@DKFZ.de
Facility:
Name:
University Hospital Ulm
Address:
City:
Ulm
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Wolfgang Janni, MD
Start date:
April 19, 2019
Completion date:
December 31, 2028
Lead sponsor:
Agency:
German Cancer Research Center
Agency class:
Other
Collaborator:
Agency:
University Hospital Heidelberg
Agency class:
Other
Collaborator:
Agency:
German Federal Ministry of Education and Research
Agency class:
Other
Source:
German Cancer Research Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05906407
