A Phase II Study of NEOADjuvant Aromatase Inhibitor and Pertuzumab/Trastuzumab (NEOADAPT)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Evidence of Pathological Response
研究概览
简要总结
This is a prospective, single-arm, phase II study of 32 evaluable patients treated with NEOADjuvant Aromatase inhibitor and Pertuzumab/Trastuzumab (NEOADAPT) without chemotherapy for hormone receptor positive (HR+), [i.e. Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+)] HER2+ localized, non-metastatic stage I - IIb 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide signed, written informed consent
- •Histologically or cytologically confirmed non-metastatic adenocarcinoma of the breast (stage I-II)
- •Candidate for curative-intent treatment
- •ER+ and/or PR+ and HER2-positive (Fluorescence In Situ Hybridization-positive or 3+ by Immunohistochemistry staining)
- •Life expectancy greater than 5 years
- •Left Ventricular Ejection Fraction > 50% at baseline (within 30 days of day 0)
- •Eastern Cooperative Oncology Group performance status ≤2
- •Absolute Neutrophil Count >1000/µL
- •Platelets ≥50,000/µL
- •Hemoglobin >8.0 g/dL,
- •Creatinine ≤3.0 x upper limit of normal (ULN)
- •Bilirubin ≤3.0 x ULN
- •Aspartate aminotransferase or Alanine aminotransferase <5.0 x ULN
- •Negative serum pregnancy test for women <12 months after the onset of menopause unless surgically sterilized
- •Agreement by women of childbearing potential and male participants with partners of childbearing potential to use a "highly effective", non-hormonal form of contraception or two "effective" forms of non-hormonal contraception by the patient and/or partner.
排除标准
- •Active infection
- •Presence of known metastases (stage IV disease)
- •Pregnant or lactating women
- •Prior chemotherapy or radiation therapy for the primary breast cancer
- •Concomitant malignancies or previous malignancies within the last 5 years except adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
- •History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
- •Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary or metabolic disease including diabetes, wound healing disorders, ulcers or bone fractures)
- •Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipated need for major surgery during the course of study treatment
- •Current known infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV) or Hepatitis C Virus (HCV)
- •Receipt of intravenous antibiotics for infection within 14 days prior to receiving study treatment
- •Current chronic daily treatment with corticosteroids (dose >10 mg/day methylprednisolone equivalent) except inhaled steroids
- •Known hypersensitivity to any of the study drugs
- •Assessment by the investigator to be unable or unwilling to comply with the requirements of the protocol
研究组 & 干预措施
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Exemestane (Drug)
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Letrozole (Drug)
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Anastrozole (Drug)
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Leuprolide Acetate (Drug)
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Pertuzumab (Drug)
Neoadjuvant Biological Therapy
Subjects will receive an aromatase inhibitor for the duration of the study [exemestane (tablet, oral, 25 mg/day), letrozole (tablet, oral, 2.5 mg/day) or anastrozole (tablet, oral, 1 mg/day)]. Premenopausal subjects will receive leuprolide acetate (11.25 mg, intramuscular injection, 3-month intervals).
Pertuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 840 mg, infused over 60-90 minutes; subsequent cycles: 420 mg, infused over 30-60 minutes).
Trastuzumab will be given by intravenous infusion in 3-week cycles until disease progression (Cycle 1 Day 0: 8 mg/kg, infused over 60-90 minutes; subsequent cycles: 6 mg/kg, infused over 30-60 minutes)
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Evidence of Pathological Response
时间窗: One year
The presence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. Pathological complete response (pCR) is defined as the absence of residual invasive cancer.
次要结局
- Measurement of Left Ventricular Ejection Fraction (LVEF)(Assessed every 12 weeks up to one year)
- Mammaprint Genomic Analysis(One year or up to 3 months after definitive surgery)
- Duration of Treatment(One year)
- Evidence of Radiographic Response(Assessed every 12 weeks up to one year)
研究者
Eugene Ahn
Principal Investigator
Midwestern Regional Medical Center