EUREKA Study: Phase 2 Study to Optimize Neoadjuvant Therapy in HER2-positive Early-stage Breast Cancer Using ctDNA and HARPS Biomarker Assay
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 7
- 主要终点
- outcomes that correspond directly to the objective(s)
研究概览
简要总结
This is an open-label phase 2 study to evaluate the pCR rate in patients diagnosed with HER2 positive breast cancer treated on an adaptive clinical trial design.
Tumors will undergo testing using a novel molecular phosphoprotein-based biomarker assay, HER2 Activation Response Predictive Signature (HARPS) to identify HARPS-positive breast cancers.
To assess 3-year invasive disease-free survival (iDFS) in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer.
To correlate changes in ctDNA with treatment outcomes in patients with HARPS-positive and HARPS-negative HER2-positive breast cancer.
To understand the changes in quality of life (QOL) measure in patients with HARPS-positive HER2-positive breast cancer treated using an adaptive neoadjuvant trial design.
详细描述
EUREKA is a phase II study that will evaluate optimization of neoadjuvant therapy in patients with stage II-III HER2-positive breast cancer. This adaptive clinical trial will enroll patients with cT2-T3 N0-2 HER2-positive breast cancer. Tumors will undergo testing using HARPS assay to identify HARPS-positive and HARPS negative HER2-positive breast cancers.
Patients with HARPS-positive HER2-positive breast cancer will be treated using an adaptive trial design to optimize neoadjuvant therapy such we are maximizing treatment efficacy while reducing risk of treatment related toxicities. Patient will be treated with dual HER2-targeted therapy (trastuzumab and pertuzumab) for 3 cycles. Treatment response will be monitored by ctDNA and MRI breast. If there is treatment response, patients will be treated with 6 cycles of trastuzumab and pertuzumab. If there is no treatment response after 6 weeks, then patients will be treated with the addition of single agent chemotherapy (docetaxel/paclitaxel/Abraxane) with trastuzumab/pertuzumab for 4 cycles followed by 2 cycles of trastuzumab and pertuzumab. Then patients will proceed with breast surgery.
Patients with HARPS-negative HER2-positive breast cancer and detectable ctDNA at time of diagnosis will be treated with 4 cycles of Taxane, platinum, trastuzumab and pertuzumab, and they will be monitored with ctDNA for ctDNA clearance. Patients who have ctDNA clearance will be treated with additional 2 cycles of the same regimen and then proceed to have surgery. If patients have detectable ctDNA at 12 weeks, then neoadjuvant therapy will be escalated to add anthracycline based regimen or trastuzumab deruxtecan (T-DXD) pe treating physicians choice.
The study will enroll a total of 50 patients- 25 patients with HARPS-positive HER2-positive early-stage breast cancer and 25 patients with HARPS-negative HARPS-positive early-stage breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria
- •Tumor size greater than 2cm or lymph node positive by imaging or clinical exam (cT2-T3 N0-2)
- •Tumors must be HER2 positive either by IHC (3+) or by IHC 2+ and FISH positive.
- •Patient must have known estrogen receptor (ER) and progesterone receptor (PR) status locally determined prior to study entry
- •Patient must have adequate tumor for HARPS testing.
- •Patients must have ctDNA collection prior to treatment on trial.
- •Patient must be able to do breast MRI as determined by the study
- •Baseline LVEF > 50% (Most recent within the last 5 years)
- •No prior history of systemic treatment with anthracyclines-based chemotherapy.
- •Adequate bone marrow function:
- •ANC ≥ 1500/uL
- •platelet count ≥ 100,000/uL
- •hemoglobin ≥ 9.0 g/dL
- •Adequate hepatic function:
- •Total bilirubin ≤ 1.5 X ULN
- •AST (SGOT) ≤ 5 X ULN
- •ALT (SGPT) ≤ 5 X ULN
- •Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.
- •Adequate renal function, Creatinine < 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.
- •Ability to understand the nature of this study protocol and give written informed consent.
- •Willingness and ability to comply with scheduled visits and treatment plans
- •Prior cancers allowed if no evidence of disease in last 5 years. Prior history of ipsilateral invasive breast cancers are not allowed.
排除标准
- •Previous treatment with chemotherapy, anti-HER2 therapy, radiation therapy, or endocrine therapy for invasive breast cancer. Exception: patients can start upto 1 cycle of HP prior to starting treatment on study.
- •cT4 and/or cN3 tumors
- •Evidence of metastatic disease by routine clinical assessment
- •Bilateral breast cancer
- •History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma
- •Left ventricular ejection fraction (LVEF) below 50% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO)
- •No active liver disease.
- •Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
- •Pre-existing sensory neuropathy > grade
- •Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
- •Serious non-healing wound, ulcer, or bone fracture
- •Patient with uncontrolled and/ or active infection with HIV, Hepatitis B or Hepatitis C.
- •Patient who has a history of allergy or hypersensitivity to any of the study drugs.
- •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
研究组 & 干预措施
HARPS POSITIVE COHORT
Arm A HARPS POSITIVE COHORT
PART A:
Patients with HARPS positive HER2 positive breast cancer will be treated with trastuzumab and pertuzumab for three cycles.
PART B:
Patients who have adequate treatment response after 3 cycles, continue trastuzumab and pertuzumab every 3 weeks for a minimum of 8 cycles in the neoadjuvant setting
ARM B:
HARPS-NEGATIVE COHORT
Patients with HARPS negative tumors must have baseline detectable ctDNA. If patients do not have detectable ctDNA, they will be taken off study. These patients will be replaced.
干预措施: Trastuzumab (Drug)
HARPS POSITIVE COHORT
Arm A HARPS POSITIVE COHORT
PART A:
Patients with HARPS positive HER2 positive breast cancer will be treated with trastuzumab and pertuzumab for three cycles.
PART B:
Patients who have adequate treatment response after 3 cycles, continue trastuzumab and pertuzumab every 3 weeks for a minimum of 8 cycles in the neoadjuvant setting
ARM B:
HARPS-NEGATIVE COHORT
Patients with HARPS negative tumors must have baseline detectable ctDNA. If patients do not have detectable ctDNA, they will be taken off study. These patients will be replaced.
干预措施: Pertuzumab (Drug)
HARPS POSITIVE COHORT
Arm A HARPS POSITIVE COHORT
PART A:
Patients with HARPS positive HER2 positive breast cancer will be treated with trastuzumab and pertuzumab for three cycles.
PART B:
Patients who have adequate treatment response after 3 cycles, continue trastuzumab and pertuzumab every 3 weeks for a minimum of 8 cycles in the neoadjuvant setting
ARM B:
HARPS-NEGATIVE COHORT
Patients with HARPS negative tumors must have baseline detectable ctDNA. If patients do not have detectable ctDNA, they will be taken off study. These patients will be replaced.
干预措施: Docetaxel (Drug)
HARPS POSITIVE COHORT
Arm A HARPS POSITIVE COHORT
PART A:
Patients with HARPS positive HER2 positive breast cancer will be treated with trastuzumab and pertuzumab for three cycles.
PART B:
Patients who have adequate treatment response after 3 cycles, continue trastuzumab and pertuzumab every 3 weeks for a minimum of 8 cycles in the neoadjuvant setting
ARM B:
HARPS-NEGATIVE COHORT
Patients with HARPS negative tumors must have baseline detectable ctDNA. If patients do not have detectable ctDNA, they will be taken off study. These patients will be replaced.
干预措施: Carboplatin (Drug)
结局指标
主要结局
outcomes that correspond directly to the objective(s)
时间窗: up to 36 months
The HARPS assay will be used to identify patients with HARPS positive and HARPS-negative HER2-positive breast cancer. Patients with Stage I-III who meet the specified eligibility criteria would be enrolled in the adaptive clinical trial. The study aims to understand whether the HARPS assay can help optimize the treatment regimen for patients diagnosed with HER2 positive breast cancer. The study will evaluate the pCR rates in patients treated with the adaptive trial regimen. The hypothesis of the study is that the adaptive treatment regimen will help improve pCR rates in patients diagnosed HER2-positive breast cancer based on the HARPS status of the tumor.
次要结局
未报告次要终点
研究者
Mridula George, MD
Associate Program Director, Breast
Rutgers, The State University of New Jersey