Overcoming Therapy Resistance in ER+ Breast Cancer Patients: a Translational Project (OVERTuRE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 2
- 主要终点
- To identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like ABC.
研究概览
简要总结
Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after >12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor in association with a CDK4/6i. Disease recurrence in <12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial.
A significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics.
Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.
详细描述
Patients presenting with a de novo diagnosis of luminal-like advanced breast cancer (ABC) or with disease recurrence after >12 months from the end of adjuvant ET, are generally candidate to a first line therapy with an aromatase inhibitor (+/- LH-RH analogue depending from the menopausal status) in association with a CDK4/6i. Disease recurrence in <12 months from the end of adjuvant ET defines the disease as "endocrine resistant" and identifies patients that should receive a first line therapy with the selective estrogen receptor degrader (SERD) Fulvestrant in association with the CDK4/6i Ribociclib, according to the results of the MONALEESA-3 trial.
The choice of the endocrine backbone and of the CDK4/6i is mostly influenced by the patient's clinical characteristics and by disease factors.
However, a significant percentage of ABC patients develops a primary resistance with disease progression within the first 6 months from the beginning of the treatment. Furthermore, another relevant percentage of patients initially responding to the therapy, will later develop a secondary resistance, thus progressing after a median of 2 years from the beginning of the treatment. Thereby, it is crucial to identify biomarkers that could be predictive of a response or a resistance to ET and/or CDK4/6i, to provide the best therapeutic strategy, tailored upon both clinico-pathological and molecular characteristics.
Numerous pathways associated with resistance to CDK4/6i have been investigated by means of liquid biopsy analysis. The aim of this study is to identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like advanced breast cancer.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease.
- •ER positive tumor ≥ 1%
- •HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio < 2.0)
- •Females, 18 years of age or older
- •Candidate to first-line endocrine therapy (LH-RH analogue for pre-menopausal women is allowed)
- •Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
排除标准
- •Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
- •Prior endocrine therapy for metastatic disease
- •Prior chemotherapy for metastatic disease
- •Patients unwilling to or unable to comply with the protocol.
- •Known CNS metastases
结局指标
主要结局
To identify potential biomarkers predictive of a clinical benefit in patients receiving a first line therapy with AI/fulvestrant (+/- LH-RH analogue) in association with a CDK4/6i for luminal-like ABC.
时间窗: up to 3 years
Mean difference in mean VAF in most frequently mutated gene found at baseline, with respect to 6 months evaluation between responders (CR-PR-SD, Complete Response - Partial Response - Stable Disease) and non-responders (PD, Progressive Disease)
次要结局
- To explore the impact of ctDNA-based biomarkers in terms of treatment resistance(from first biomarker assessment until objective PD or end of follow-up, up to 3 years)
- To explore the impact of ctDNA-based biomarkers in terms of survival(from beginning of the therapy until death from any cause or end of follow-up, up to 3 years)
- Mean difference in mean VAF in most frequently mutated gene found at baseline, between baseline and progression in non-responders (PD, Progressive Disease)(up to 3 years)