A Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies

NCT06274515 | Recruiting Phase 4

• 1 other identifier: WO44977
• Study Type: interventional
• Target: 320
• Locations: 8 countries
• Sites: 28

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (10)

• 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 HER2 gene copy number 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 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 genes related to endocrine 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

Study Arms (2)

Mechanisms of Acquired Resistance

EXPERIMENTAL

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.

Procedure: Tumor Tissue and Blood Draw

Mechanisms of Primary Resistance

EXPERIMENTAL

Participants with breast cancer who have a progressing tumor lesion while on anti-cancer therapy will be assigned to one of 2 cohorts.

Procedure: Tumor Tissue and Blood Draw

Interventions

Tumor Tissue and Blood Draw PROCEDURE

Participants will have their blood drawn on the day a tissue sample is taken from a progressive tumor lesion.

Mechanisms of Acquired Resistance; Mechanisms of Primary Resistance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (28)

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

AZ KLINA

Brasschaat, 2930, Belgium

RECRUITING

CHU de Liège (Sart Tilman)

Liège, 4000, Belgium

RECRUITING

AZ Delta (Campus Rumbeke)

Roeselare, 8800, Belgium

RECRUITING

Aalborg Universitetshospital

Aalborg, 9000, Denmark

RECRUITING

Sjællands Universitetshospital, Næstved

Næstved, 4700, Denmark

RECRUITING

Helsinki University Central Hospital

Helsinki, 00029, Finland

RECRUITING

Tampere University Hospital

Tampere, 33520, Finland

RECRUITING

St. Elisabeth Krankenhaus Köln GmbH

Cologne, 50935, Germany

RECRUITING

KEM/Evang. Kliniken Essen Mitte gGmbH

Essen, 45136, Germany

RECRUITING

ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76135, Germany

RECRUITING

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

RECRUITING

Universitätsfrauenklinik Ulm

Ulm, 89075, Germany

RECRUITING

I.R.S.T Srl IRCCS

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Azienda Ospedaliero - Universitaria di Modena Policlinico

Modena, Emilia-Romagna, 41110, Italy

RECRUITING

RCCS - Centro di Riferimento

Aviano (PN), Friuli Venezia Giulia, 33081, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

RECRUITING

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, 20132, Italy

RECRUITING

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy, 20133, Italy

RECRUITING

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, 20141, Italy

RECRUITING

Oslo university hospital Radiumhospitalet

Oslo, 0424, Norway

WITHDRAWN

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

HM Sanchinarro ? CIOCC

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

Basingstoke and North Hampshire Hospital

Basingstoke, RG24 9NA, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

RECRUITING

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: WO44977 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: February 23, 2024
• Study Start: April 2, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); DK (2); GB (3); FI (2); DE (5); IT (7); BE (4); ES (4)