A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard (Neo)Adjuvant Treatment in Patients With Operable HER2+/HR+ Breast Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 257
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR)
研究概览
简要总结
This is a prospective, phase IIa, multicenter, randomized, open-label study comparing a pre-surgical combination of trastuzumab and pertuzumab with concurrent weekly paclitaxel chemotherapy or endocrine therapy given for 12 weeks with a quality of life assessment for 40 additional weeks in patients with operable HER2+/HR+ breast cancer.
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 older
- •Histologically confirmed unilateral primary invasive carcinoma of the breast
- •Patients must qualify for neoadjuvant treatment as follows:
- •No clinical evidence for distant metastasis (M0)
- •Clinical cT1c-T4a-c (participation of patients with tumors > cT2 is strongly recommended) and no evidence for distant metastases (M0)
- •All clinical N (participation of patients with cN+, also in case of cT1c, is strongly recommended)
- •Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH
- •Patients need to fulfill adequate blood count and organ function to receive chemotherapy (see exclusion criteria).
- •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 registration in premenopausal patients
- •Patients of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) non-hormonal contraceptive measures during the study treatment and for 6 months following the last dose of study treatment (trastuzumab and pertuzumab) such as:
- •Intrauterine device (IUD)
- •bilateral tubal occlusion
- •vasectomised partner
- •sexual abstinence
- •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
- •LVEF > 55%; LVEF within normal limits of each institution measured by echocardiography (within 42 days prior to randomization)
- •Normal ECG (within 42 days prior to randomization)
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
- •Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project within 30 days prior to study entry is excluded
- •Male breast cancer
- •Concurrent pregnancy
- •Breastfeeding
- •Sequential breast cancer
- •Reasons indicating risk of poor compliance
- •Known polyneuropathy ≥ grade 2
- •Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to:
- •Uncompensated chronic heart failure or systolic dysfunction (LVEF < 55%, CHF NYHA classes II-IV),
- •unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block,
- •Angina pectoris within the last 6 months requiring anti-anginal medication,
- •Clinically significant valvular heart disease,
- •Evidence of myocardial infarction on electrocardiogram (ECG),
- •Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mm Hg).
- •Inadequate organ function including but not confined to:
- •hepatic impairment (Child Pugh Class C)
- •pulmonary disease (severe dyspnea at rest requiring oxygen therapy)
- •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
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Perjeta Injectable Product (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Herceptin (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Tamoxifen (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Paclitaxel (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Epirubicin (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Cyclophosphamide (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Anastrozole (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Letrozole (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Exemestane (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Leuprorelin acetate (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Goserelin (Drug)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Biopsy (Diagnostic Test)
Paclitaxel+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with standard Taxane chemotherapy.
Adjuvant Therapy: Standard of care
干预措施: Surgery (Procedure)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Perjeta Injectable Product (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Herceptin (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Anastrozole (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Epirubicin (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Cyclophosphamide (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Letrozole (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Exemestane (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Paclitaxel (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Tamoxifen (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Leuporelin acetate (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Goserelin (Drug)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Biopsy (Diagnostic Test)
Endocrine+Trastuzumab+Pertuzumab
Neoadjuvant therapy: Trastuzumab and Pertuzumab in a 3-weekly schedule in combination with endocrine therapy.
Adjuvant Therapy: Standard of care
干预措施: Surgery (Procedure)
结局指标
主要结局
Pathological complete response (pCR)
时间窗: 14 weeks after start of therapy treatment
14 weeks after start of therapy treatment, tumor and lymph node biopsy is performed to reach the primary endpoint of pathological complete response (pCR) which is defined as the absence of residual invasive cancer of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (ypT0/is ypN0 in the current AJCC staging system). As secondary endpoint, also other response states will be taken into account: no invasive tumor in the complete resected breast specimen irrespective of the lymph node state following completion of neoadjuvant systemic therapy (ypT0/is, any ypN).
次要结局
- Health-related quality of life using EORTC QBL-BR-23 scale(During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first)
- Health-related quality of life using EQ5D-5L scale(During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first)
- Health-related quality of life using EORTC QLQ-C30 scale(During the neoadjuvant treatment phase at baseline (week 1) and at week 13. In the adjuvant therapy phase, every 3 month, up to 12 months (from date of randomization) or date of drop out, whatever comes first)
- Tumor size reduction by mammography(at screening visit and 12 weeks after start of therapy treatment)
- Overall survival(From date of randomization until the date of death from any cause, assessed up to 60 months)
- Tumor size reduction by palpation and ultrasound(at screening visit and 4, 7 and 13 weeks after start of therapy treatment)
- Number of mastectomies(14 weeks after start of therapy treatment)
- Ki67 level(4 weeks after start of therapy treatment)
- Duration of invasive disease-free survival(From date of treatment allocation until the date of first documented progression or secondary tumor or date of death from any cause, whichever came first, assessed up to 60 months (study duration including follow up))
- cDNA composition(at baseline, 3 weeks, 4 weeks and 6, 18, 24, 36 48 and 60 months after start of therapy treatment)