A Multi Cohort Translational Research Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies
Overview
- Phase
- Phase 4
- Intervention
- Tumor Tissue and Blood Draw
- Conditions
- Breast Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 320
- Locations
- 49
- Primary Endpoint
- Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2)
- Status
- Recruiting
- Last Updated
- 26 days ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion 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
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
Arms & Interventions
Mechanisms of Acquired Resistance
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.
Intervention: Tumor Tissue and Blood Draw
Mechanisms of Primary Resistance
Participants with breast cancer who have a progressing tumor lesion while on anti-cancer therapy will be assigned to one of 2 cohorts.
Intervention: Tumor Tissue and Blood Draw
Outcomes
Primary Outcomes
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 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 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 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 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 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