Clinical trial NCT06274515: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2024-02-23
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2)
timeFrame: At least 6 months
measure: Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohorts H1 and H2)
timeFrame: At least 6 months
measure: Changes from baseline in estrogen receptor (ER) protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2)
timeFrame: At least 6 months
measure: Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohort H3)
timeFrame: Less than 6 months
measure: Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohort H3)
timeFrame: Less than 6 months
measure: Changes from baseline in ER protein levels measured at the time of disease progression/recurrence (Cohort H3)
timeFrame: Less than 6 months
measure: Changes from baseline in genes related to CDK4/6 resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1)
timeFrame: At least 6 months
measure: Changes from baseline in genes related to endocrine resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1)
timeFrame: At least 6 months
measure: Changes from baseline in tumor immune microenvironment (PD-L1 and TILs, Cohort T1)
timeFrame: At least 6 months
measure: Changes from baseline in immune phenotype (PD-L1 and TILs, Cohort T1)
timeFrame: At least 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
city: Naestved
country: Denmark
facility: Sjællands Universitetshospital, Næstved
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Essen
country: Germany
facility: KEM/Evang. Kliniken Essen Mitte gGmbH
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken Karlsruhe, Vincentius-Diakonissen-Kliniken gAG
city: Koeln
country: Germany
facility: St. Elisabeth Krankenhaus Köln GmbH
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
city: Meldola
country: Italy
facility: I.R.S.T Srl IRCCS
state: Emilia-Romagna
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria di Modena Policlinico
state: Emilia-Romagna
city: Aviano (PN)
country: Italy
facility: RCCS - Centro di Riferimento
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO)
state: Lombardia
city: Oslo
country: Norway
facility: Oslo university hospital Radiumhospitalet
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: HM Sanchinarro ? CIOCC
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: