ECLECTIC: EstroTEP and Circulating Biomarkers to Determine the Optimal Second Line Therapy for ER-positive HER2-negative Metastatic Breast Cancer Patients
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 33
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
Eclectic is a strategy trial; once the class of treatment (endocrine therapy or chemotherapy) has been allocated according to 16α-18F-fluoro-17β-oestradiol (18F-FES) Positron Emission Tomography/Computed Tomography (PET/CT) results and circulating tumor biomarkers, clinicians will decide which treatment to use.
详细描述
All patients deemed eligible for a second line endocrine therapy will undergo a 18F-FES PET/CT scan and circulating tumor biomarkers assessment (circulating tumor cells (CTC) and, if not available, circulating tumor DNA (ctDNA)). All 18F-FES PET/CT scan will be anonymized and reviewed centrally, and compared to the 18Fluorodeoxyglucose (18F-FDG) PET/CT results before treatment initiation; circulating biomarkers status will be assessed centrally and will remain blinded to investigator and patients.
Endocrine therapy in Arm A and C may consist in single agent endocrine therapy or in combination with targeted therapy. Luteinizing Hormone-Releasing Hormone (LH-RH) agonist will be used in combination with endocrine therapy whenever appropriate and per label. Chemotherapy in Arm B may consist in single agent chemotherapy, poly-chemotherapy, or antibody-drug conjugates. Patients who are eligible (per drug label) may receive Poly-adenosine-5'-diphosphate-ribose Polymerase (PARP) inhibitor if allocated to Arm B.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Metastatic invasive breast carcinoma of no special type.
- •Females and males of age ≥18 years.
- •Life expectancy > 3 months.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Estrogen Receptor (ER)-positive (≥10%) and HER2-negative (ASCO/College of American Pathologists guidelines) breast cancer, per local assessment on the most recent breast cancer tissue examined.
- •Tumor block Formalin-Fixed Paraffin-Embedded (primary tumor or metastasis) available.
- •Patients whose disease has progressed on first line endocrine therapy with aromatase inhibitor and CDK4/6 inhibitor and who are deemed eligible, per investigator assessment, to a second line endocrine therapy. The progression on first line endocrine therapy with aromatase inhibitor and CDK4/6 inhibitor must have occurred after more than 6 months on treatment.
- •Patients with available 18F-FDG PET/CT imaging
- •Evaluable disease per RECIST criteria and measurable disease per PERCIST criteria.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and any protocol-related procedures including screening evaluations.
- •Signed informed consent.
- •Patient affiliated to a social security system.
排除标准
- •Other breast cancer subtype (e.g. invasive lobular breast carcinoma).
- •One or more prior line of chemotherapy in the metastatic setting.
- •Any other systemic treatment given at metastatic disease than the first line therapy with aromatase inhibitor and CDK4/6 inhibitor.
- •Visceral crisis, per investigator's assessment.
- •Liver-only metastases.
- •Prior exposure to any authorized or experimental agent degrading the estrogen receptor (fulvestrant, oral SERDs, PROTAC, etc).
- •Pregnancy or lactation period.
- •In women of childbearing potential or premenopausal women or women with amenorrhea of less than 12 months, without adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization; LH-RH agonist cannot be considered as an efficient contraceptive measure), positive urinary or serum pregnancy test 72 hours before 18F-FES PET/CT.
- •Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Patients with a history of CNS metastases or cord compression are eligible if they have been treated with local therapy (e.g., radiotherapy, stereotactic surgery) and are clinically stable and off anticonvulsants and steroids for at least 4 weeks before treatment start.
- •History of previous cancer or hematological malignancy within 3 years preceding patient enrollment in the trial. Multiple primary breast cancers (controlateral/ipsilateral cancers/local relapses) are allowed pending all tumors were ER+ HER2-.
- •Persons deprived of their freedom or under guardianship or incapable of giving consent.
研究组 & 干预措施
Arm A: Endocrine therapy
- Patients in whom all tumor sites display a FES SUVmax ≥2 AND who have low levels of circulating tumor biomarkers will be treated with endocrine therapy.
- Patients in whom 18F-FES PET shows an heterogenous uptake, with one or maximum two tumor sites with low FES uptake (SUVmax <2) that represent less than 20% of all tumor sites and are deemed accessible to local treatment (e.g. stereotactic radiation therapy or another equivalent local therapy) will be treated, if they have low levels of circulating tumor biomarkers, by 2nd line endocrine therapy in Arm A, combined with the local treatment of FES-negative lesions.
干预措施: Endocrine therapy (Combination Product)
Arm A: Endocrine therapy
- Patients in whom all tumor sites display a FES SUVmax ≥2 AND who have low levels of circulating tumor biomarkers will be treated with endocrine therapy.
- Patients in whom 18F-FES PET shows an heterogenous uptake, with one or maximum two tumor sites with low FES uptake (SUVmax <2) that represent less than 20% of all tumor sites and are deemed accessible to local treatment (e.g. stereotactic radiation therapy or another equivalent local therapy) will be treated, if they have low levels of circulating tumor biomarkers, by 2nd line endocrine therapy in Arm A, combined with the local treatment of FES-negative lesions.
干预措施: Endocrine therapy combined with the local treatment of FES-negative lesions (Combination Product)
Arm B: Chemotherapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
干预措施: Endocrine therapy (Combination Product)
Arm B: Chemotherapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
干预措施: Chemotherapy (Combination Product)
Arm C: Endocrine therapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
干预措施: Endocrine therapy (Combination Product)
Arm C: Endocrine therapy
All other patients, i.e. (i) patients in whom most or ≥3 lesions display a FES SUVmax <2 that are not amenable to local treatment, (ii) patients with high levels of circulating tumor biomarkers, will be randomized between chemotherapy in Arm B and endocrine therapy in Arm C.
干预措施: Chemotherapy (Combination Product)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 54 months
PFS is defined as the time from randomization to progression (per RECIST 1.1) or death, among randomized patients.
次要结局
- Overall survival (OS)(54 months)
- Clinical benefit rate (CBR)(24 weeks)
- Efficacy criteria: ORR at 24 weeks(24 weeks)
- Safety and toxicity and their relationship to study treatment(54 months)
- EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) after 2 months of treatment(2 months)
- Progression-Free survival (PFS)(54 months)
- Objective response rate (ORR)(54 months)
- Efficacy criteria: PFS at 24 weeks(24 weeks)
- Efficacy criteria: CBR at 24 weeks(24 weeks)
- Efficacy criteria: OS at 24 weeks(24 weeks)