A Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies

Official title

A Multi Cohort Translational Research Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies

Overview

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.

Interventions

• Procedure Tumor Tissue and Blood Draw
  Participants will have their blood drawn on the day a tissue sample is taken from a progressive tumor lesion.

Primary outcome measures

• Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2) [Time frame: At least 6 months]
• Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohorts H1 and H2) [Time frame: 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) [Time frame: At least 6 months]
• Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohort H3) [Time frame: Less than 6 months]
• Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohort H3) [Time frame: Less than 6 months]
• Changes from baseline in ER protein levels measured at the time of disease progression/recurrence (Cohort H3) [Time frame: Less than 6 months]
• Changes from baseline in genes related to CDK4/6 resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1) [Time frame: At least 6 months]
• Changes from baseline in genes related to endocrine resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1) [Time frame: At least 6 months]
• Changes from baseline in tumor immune microenvironment (PD-L1 and TILs, Cohort T1) [Time frame: At least 6 months]
• Changes from baseline in immune phenotype (PD-L1 and TILs, Cohort T1) [Time frame: At least 6 months]

Eligibility criteria

General Inclusion Criteria:

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 7 centers

• I.R.S.T Srl IRCCS — Meldola
• Azienda Ospedaliero - Universitaria di Modena Policlinico — Modena
• RCCS - Centro di Riferimento — Aviano (PN)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Ospedale San Raffaele S.r.l. - PPDS — Milan
• Irccs Istituto Nazionale Dei Tumori (Int) — Milan
• Irccs Istituto Europeo Di Oncologia (IEO) — Milan

Germany · 5 centers

• St. Elisabeth Krankenhaus Köln GmbH — Cologne
• KEM/Evang. Kliniken Essen Mitte gGmbH — Essen
• ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG — Karlsruhe
• Universitätsklinikum Mannheim — Mannheim
• Universitätsfrauenklinik Ulm — Ulm

Belgium · 4 centers

• Institut Jules Bordet — Anderlecht
• AZ KLINA — Brasschaat
• CHU de Liège (Sart Tilman) — Liège
• AZ Delta (Campus Rumbeke) — Roeselare

Spain · 4 centers

• Hospital Universitario 12 de Octubre — Madrid
• HM Sanchinarro ? CIOCC — Madrid
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Clínico Universitario de Valencia — Valencia

United Kingdom · 3 centers

• Basingstoke and North Hampshire Hospital — Basingstoke
• Imperial College Healthcare NHS Trust — London
• Christie Hospital NHS Trust — Manchester

Denmark · 2 centers

• Aalborg Universitetshospital — Aalborg
• Sjællands Universitetshospital, Næstved — Næstved

Finland · 2 centers

• Helsinki University Central Hospital — Helsinki
• Tampere University Hospital — Tampere

Norway · 1 center

• Oslo university hospital Radiumhospitalet — Oslo

Identifiers

NCT: NCT06274515 · WO44977

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗