Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients With Operable or Locally Advanced/Inflammatory HER2-positive Breast Cancer (ImmunHER)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 65
- 试验地点
- 21
- 主要终点
- Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph)
研究概览
简要总结
Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients with Operable or Locally Advanced /Inflammatory HER2-positive Breast Cancer (ImmunHER)
详细描述
Women with histologically confirmed HER2-positive breast cancer with locally advanced, inflammatory,or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Previously untreated, infiltrating primary breast cancer with locally advanced, inflammatory, or early stage tumor (either greater than 2 cm in diameter or node positive) with no evidence of metastatic disease.
- •HER2 positivity (either immunohistochemistry 3+ or fluorescent in situ hybridization amplification).
- •Age 18 or older.
- •Eastern Cooperative Oncology Group performance status of 0 to
- •Availability of tumor tissue for biologic and molecular examination before starting primary treatment.
- •Left ventricular ejection fraction within the institutional range of normal.
- •Normal organ and marrow function.
- •Adequate contraception methods for women of childbearing potential.
- •Prior diagnosis of cancer is allowed as long as patient is free of disease and has been off treatment for the prior malignancy for a minimal interval of 3 years.
- •Written informed consent.
排除标准
- •Either stage I or IV breast cancer.
- •Prior trastuzumab or pertuzumab.
- •Any prior chemotherapy.
- •Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
- •Undergone major surgery (e.g., intrathoracic, intra-abdominal or intra-pelvic) 4 weeks prior to starting study drug or who have not recovered from side effects of such surgery.
- •Breast radiotherapy prior to starting study.
- •Known hypersensitivity to the investigational drugs or any of their excipients.
- •Evidence of any disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an GOIRC-01-2016 ImmunHER Protocol Version 1.0, 11 April 2016 Page 6 of 140 investigational drug, or puts the patient at high risk for treatment-related complications.
- •Moderate/severe hepatic impairment (Child- Pugh B/C).
- •Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Concurrent malignancy or malignancy within 3 years prior to study enrollment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or insitu carcinoma of the uterine cervix.
- •Pregnancy or breastfeeding (breast feeding should be discontinued to be enrolled in the study).
- •Women of childbearing potential that refusal to adopt adequate contraceptive measures.
- •Unwilling or unable to comply with the protocol. -
研究组 & 干预措施
Group A
Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.
After surgery, study patients will receive trastuzumab IV x 14 cycles
干预措施: Trastuzumab IV (Biological)
Group A
Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.
After surgery, study patients will receive trastuzumab IV x 14 cycles
干预措施: Pertuzumab (Biological)
Group A
Trastuzumab IV (8 mg/kg loading dose, followed by 6 mg/kg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles.
After surgery, study patients will receive trastuzumab IV x 14 cycles
干预措施: Docetaxel (Drug)
Group B
Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles. After surgery, study patients will receive trastuzumab SC x 14 cycles
干预措施: Trastuzumab SC (Biological)
Group B
Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles. After surgery, study patients will receive trastuzumab SC x 14 cycles
干预措施: Pertuzumab (Biological)
Group B
Trastuzumab SC (fixed dose of 600 mg) plus pertuzumab IV (840 mg loading dose, followed by 420 mg) plus docetaxel (75 mg/m2)*, every 3 weeks for 4 cycles. After surgery, study patients will receive trastuzumab SC x 14 cycles
干预措施: Docetaxel (Drug)
结局指标
主要结局
Tumor Infiltrating lymphocites (TIL) rate on residual disease after either IV trastuzumab or SC trastuzumab (see related paragraph)
时间窗: 6 months after last patient in
stromal lymphocytes will be scored quantitatively on H\&E stained whole-tumor slides as a continuous variable expressed as stromal percentage area within the tumor boundaries. For tumors with heterogeneous TILs, median values will be calculated from multiple counts from different tumor areas. Intra-epithelial TILs will also be recorded as well as tertiary lymphoid structures. Tumor regression will be scored based on recommended criteria.
次要结局
- HRQOL during study treatment based on FACT-B(at baseline, and 6 months after last patient in)
- Associations between biomarkers (TIL, Tumor specific lymphocyte cell activity (TLA), and Fc-gamma-R polymorphisms) and between each biomarker with clinical outcome variables.(at baseline, 6 months and 5 years after last patient in)
- Complete pathological response rate by treatment arm(6 months after last patient in)
- Frequency of toxicity Events: frequency of moderate and severe toxicity events and drop-out rate due to theraphy related toxicity (NCICommon Toxicity Criteria v 4.0)(3.5 years)
- 5-year disease-free survival by treatment arm between treatment arms(5 years)