A Multi Cohort Translational Research Study to Investigate Mechanisms of Resistance to Breast Cancer Therapies
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 320
- 试验地点
- 48
- 主要终点
- Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Tumor Tissue and Blood Draw (Procedure)
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.
干预措施: Tumor Tissue and Blood Draw (Procedure)
结局指标
主要结局
Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohorts H1 and H2)
时间窗: 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)
时间窗: At least 6 months
Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohorts H1 and H2)
时间窗: At least 6 months
Changes from baseline in genes related to endocrine resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1)
时间窗: At least 6 months
Changes from baseline in HER2 protein levels measured at the time of disease progression/recurrence (Cohort H3)
时间窗: Less than 6 months
Changes from baseline in HER2 gene copy number measured at the time of disease progression/recurrence (Cohort H3)
时间窗: Less than 6 months
Changes from baseline in ER protein levels measured at the time of disease progression/recurrence (Cohort H3)
时间窗: Less than 6 months
Changes from baseline in genes related to CDK4/6 resistance (incl. cell cycle alterations and tyrosine kinase receptors, Cohort R1)
时间窗: At least 6 months
Changes from baseline in tumor immune microenvironment (PD-L1 and TILs, Cohort T1)
时间窗: At least 6 months
Changes from baseline in immune phenotype (PD-L1 and TILs, Cohort T1)
时间窗: At least 6 months
次要结局
未报告次要终点