A Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies
- Conditions
- Breast Cancer
- Interventions
- Procedure: Tumor Tissue and Blood Draw
- Registration Number
- NCT06274515
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate mechanisms of resistance to anti-breast cancer therapies in tumor and blood samples from participants with human epidermal growth factor receptor (HER2) positive, hormone receptor (HR) positive or triple negative breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 320
- Willingness to undergo a procedure to obtain tumor tissue (e.g. biopsy) and blood draw
- Diagnosis of HER2+, HR+ (for cohort R1) or triple negative breast cancer (for cohort T1) as per local assessment
- Availability of an archival tumor tissue (most recent pre-treatment tumor tissue is preferred)
- Unequivocally growing tumor lesion (progressive lesion) that is accessible for resection, excision or core needle biopsy
- Discontinuation of prior anti-cancer treatment outlined below should not be longer than 4 weeks from participation in this study
Inclusion criteria for participants in the cohorts studying acquired resistance
- Participant had undergone regular monitoring for disease progression as per local practice (preferably every 3-6 months) while on most recent breast cancer therapy
- Accessible tumor lesion that newly appeared or a lesion that started to regrow while the participant was at least 6 months on therapy
Inclusion criteria for participants in the cohort studying primary resistance
- Accessible tumor lesion that continued to increase in size or a newly appearing lesion (as confirmed by routine tumor assessment) while treated for at least 4 weeks but less than 6 months on therapy
- Any risks factors that increase the risk of complications associated with the procedure to obtain tumor tissue (e.g. bleeding disorders)
- Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
- Participant has started treatment with subsequent anti-cancer therapy
- Participants whose progressive tumor lesion that is targeted for biopsy/resection is in the bone
- Discontinuation of treatment was due to a reason other than disease progression
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mechanisms of Acquired Resistance Tumor Tissue and Blood Draw Participants with breast cancer who have a newly appearing or recurrent metastatic lesion while on anti-cancer therapy will be assigned to one of 3 cohorts. Mechanisms of Primary Resistance Tumor Tissue and Blood Draw Participants with breast cancer who have a progressing tumor lesion while on anti-cancer therapy will be assigned to one of 2 cohorts.
- Primary Outcome Measures
Name Time Method Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2) At least 6 months Changes from baseline in estrogen receptor (ER) protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2) At least 6 months Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohorts H1 and H2) At least 6 months Changes from baseline in genes related to endocrine resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1) At least 6 months Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohort H3) Less than 6 months Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohort H3) Less than 6 months Changes from baseline in ER protein levels measured at the time of disease progression/recurrence (Cohort H3) Less than 6 months Changes from baseline in genes related to CDK4/6 resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1) At least 6 months Changes from baseline in tumor immune microenvironment (PD-L1 and TILs, Cohort T1) At least 6 months Changes from baseline in immune phenotype (PD-L1 and TILs, Cohort T1) At least 6 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (26)
Aalborg Universitetshospital
🇩🇰Aalborg, Denmark
Sjællands Universitetshospital, Næstved
🇩🇰Naestved, Denmark
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
St. Elisabeth Krankenhaus Köln GmbH
🇩🇪Koeln, Germany
Universitätsklinikum Mannheim
🇩🇪Mannheim, Germany
I.R.S.T Srl IRCCS
🇮🇹Meldola, Emilia-Romagna, Italy
Irccs Istituto Europeo Di Oncologia (IEO)
🇮🇹Milano, Lombardia, Italy
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
CHU Sart-Tilman
🇧🇪Liège, Belgium
KEM/Evang. Kliniken Essen Mitte gGmbH
🇩🇪Essen, Germany
ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG
🇩🇪Karlsruhe, Germany
RCCS - Centro di Riferimento
🇮🇹Aviano (PN), Friuli-Venezia Giulia, Italy
Irccs Istituto Nazionale Dei Tumori (Int)
🇮🇹Milano, Lombardia, Italy
Oslo university hospital Radiumhospitalet
🇳🇴Oslo, Norway
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
HM Sanchinarro ? CIOCC
🇪🇸Madrid, Spain
Hospital ClÃnico Universitario de Valencia
🇪🇸Valencia, Spain
AZ Delta (Campus Rumbeke)
🇧🇪Roeselare, Belgium
Azienda Ospedaliero - Universitaria di Modena Policlinico
🇮🇹Modena, Emilia-Romagna, Italy
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Ospedale San Raffaele S.r.l. - PPDS
🇮🇹Milano, Lombardia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, United Kingdom
Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom