A Prospective, Randomized Multicenter, Open-label Comparison of Preoperative Trastuzumab Emtansine (T-DM1) With or Without Standard Endocrine Therapy vs. Trastuzumab With Standard Endocrine Therapy Given for Twelve Weeks in Patients With Operable HER2+/HR+ Breast Cancer Within the ADAPT Protocol.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 380
- 试验地点
- 2
- 主要终点
- Evaluation of dynamic testing (based on proliferation/apoptosis changes in serial biopsy and imaging by MRI) after three weeks of treatment as a surrogate parameter for response.
研究概览
简要总结
Trial to optimize neoadjuvant therapy for HER overexpression and co-expressing of hormone receptors(ER and/or PR) breast cancer (HEr2+/HR+).
A new high potential trastuzumab conjugate T-DM1(trastuzumab was linked with the cytotoxic agent mertansine DM1)was tested with endocrine therapy and without against a standard arm with trastuzumab and endocrine therapy.
详细描述
the neoadjuvant therapy Patients with HER2+/HR+ (HER2+ and ER+ and/or PR+) tumor will receive single agent T-DM1 for 12 weeks (3,6 mg/kg q3w) with or without standard endocrine therapy (tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if not contraindications are present, in a standard daily dosage). The control group will receive trastuzumab in 3-weekly schedule (8 mg/kg as loading dose and then 6 mg/kg q3w) in combination with the same standard endocrine therapy, if no contraindications are existent.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
- •Histologically confirmed unilateral primary invasive carcinoma of the breast
- •Clinical T1 - T4 (except inflammatory breast cancer)
- •All clinical N (cN)
- •No clinical evidence for distant metastasis (M0)
- •Known HR status and HER2 status (local pathology) Tumor block available for central pathology review
- •Performance Status ECOG ≤ 1 or KI ≥ 80%
- •Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
- •Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
- •The patient must be accessible for treatment and follow-up
- •Additional Inclusion criteria for participation in the HER2+/HR+ sub-protocol:
- •Confirmed ER and/or PR positive and HER2+ by central pathology
- •Clinical cT1c - T4a-c (participation of patients with tumors >cT2 is strongly recommended)
- •All clinical N (participation of patients with cN0, if cT1c is strongly recommended)
- •Patients must qualify for neoadjuvant treatment
- •LVEF > 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment)
排除标准
- •Known hypersensitivity reaction to the compounds or incorporated substances
- •Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
- •Non-operable breast cancer including inflammatory breast cancer
- •Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
- •Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
- •Male breast cancer
- •Concurrent pregnancy; patients of childbearing potential must implement
- •a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
- •Breast feeding woman
- •Sequential breast cancer
- •Reasons indicating risk of poor compliance Patient not able to consent
- •Additional Exclusion Criteria for participation in the HER2+/HR+ sub-protocol:
- •Known polyneuropathy ≥ grade 2
- •Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study
- •Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)
- •Uncompensated cardiac function (current unstable ventricular arrhythmia
- •requiring treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial infarction or unstable angina pectoris within 6 months of enrollment, history of severe hypertension, CAD - coronary artery disease)
- •Severe dyspnea
- •Pneumonitis
- •Abnormal blood values:
- •Thrombocytopenia > CTCAE grade 1
- •Increases in ALT/AST > CTCAE grade 1
- •Hypokalaemia > CTCAE grade 1
- •Neutropenia > CTCAE grade 1
- •Anaemia > CTCAE grade 1
研究组 & 干预措施
T-DM1
single agent T-DM1 for 12 weeks (3,6 mg/kg q3w)
干预措施: T-DM1 (Drug)
T-DM1 + endocrine therapy
Single agent T-DM1 for 12 weeks (3,6 mg/kg q3w) with standard endocrine therapy (tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if no contraindications are present, in a standard daily dosage).
干预措施: T-DM1 (Drug)
Trastuzumab + endocrine therapy
The control group will receive trastuzumab in 3-weekly schedule (8 mg/kg as loading dose and then 6 mg/kg q3w)with endocrine therapy tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if not contraindications are present, in a standard daily dosage).
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Evaluation of dynamic testing (based on proliferation/apoptosis changes in serial biopsy and imaging by MRI) after three weeks of treatment as a surrogate parameter for response.
时间窗: after 3 weeks of treamtment
Response: pCR (residual cancer burden (RCB) 0-1) or resistance/low response (RCB II-III or progressive disease)
Comparison of the pCR rates in patients with HER2+/HR+ breast cancer treated by preoperative T-DM1 with or without standard endocrine therapy or trastuzumab with endocrine therapy.
时间窗: After 12 weeks
pCR will be measured after 12 weeks of randomized treatment.
次要结局
- Overall survival(5 year after treamtment)
- Toxicity/cardiac safety(5 years after treatment)
- Overall safety in the three treatment arms(5 years after treatment)
- Health-related quality of life (HRQL)(After 5 year after treatment of last patient)
- Evaluation of dynamic test regarding prediction of 5-year event-free survival (EFS)(5 year after treatment)