PREDIX HER2 - Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer. Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 202
- 试验地点
- 7
- 主要终点
- Pathological objective response to primary medical treatment
研究概览
简要总结
The purpose of this trial is to evaluate efficacy and toxicity of either the combination of docetaxel, trastuzumab sc and pertuzumab (arm A) or trastuzumab emtansin (arm B). Switch of therapy to the opposite treatment alternative is applicable in case of lack of response after two courses of treatment, or for medical reasons under exceptional circumstances (drug reaction, other medical conditions) at any point. After termination of the primary treatment follow-up for five years.
A translational subprotocol is a mandatory part of the study protocol, with exception for the use of PET-CT evaluations.
详细描述
Patients with HER2-positive tumors >20 mm or verfied regional lymph node metastases are randomized to either arm A, the combination of docetaxel, trastuzumab sc (Herceptin SC®) and pertuzumab (Perjeta®) or arm B, trastuzumab emtansin (Kadcyla®). Switch to the opposite treatment is performed in case of lack of response after evaluations with mammography and ultrasound, alternatively MRI breast after the 2nd, 4th and 6th course of treatment.
Postoperative treatment, trastuzumab, radiotherapy, eventual endocrine treatment) according to standard guidelines. Structured follow-up visits yearly for five years, including reporting of persistent treatment-related toxicity, HRQoL, recurrence and death.
The trial contains also a translational subprotocol:
- PET-CT using FDG, confined to the chest, is performed before start, and after the 2nd and 6th course (functional imaging, optional).
- Core biopsies from the tumor are collected before start and after the 2nd course of treatment. If residual tissue is available, samples are collected from the surgical sample
- Blood samples are collected repeatedly during the ongoing treatment and yearly follow-up
- FNAs from metastases in case of recurrence during follow-up
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
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Patients with breast cancer confirmed by histology, characterized by immunohistochemistry for ER, PR, HER2 and proliferation marker
- •Tumor and blood samples available. HER2 type confirmed by ISH
- •Age 18 years or older. Elderly patients in condition adequate for planned therapy
- •Primary breast cancer >20mm in diameter and/or verified lymph node metastases
- •Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
- •ECOG performance status 0-1
- •Primary breast cancer as defined in p. 5 plus at most 2 morphologically characterized well-defined distant metastases accessible for stereotactic radiotherapy, provided that this treatment is available
排除标准
- •Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
- •Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix
- •Patients in child-bearing age without adequate contraception
- •Pregnancy or lactation
- •Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders
研究组 & 干预措施
A standard treatment
docetaxel + trastuzumab sc + pertuzumab. Treatment with all three drugs is given on day 1, repeated every three weeks. Six courses of preoperative treatment. Response evaluations after every 2nd course. In case of no change (NC), treatment is switched to arm B.
Postoperatively, patients receive 2 courses of treatment with the combination epirubicin + cyclophosphamide (EC), followed by adjuvant trastuzumab, radiotherapy, eventually endocrine treatment.
干预措施: docetaxel + trastuzumab sc + pertuzumab (Drug)
B experimental treatment
trastuzumab emtansine. Treatment is given on day 1, repeated every three weeks. Six courses of preoperative treatment. Response evaluations after every 2nd course. In case of no change (NC), treatment is switched to arm A.
Postoperatively, patients receive 4 courses of treatment with the combination epirubicin + cyclophosphamide (EC), followed by adjuvant trastuzumab, radiotherapy, eventually endocrine treatment.
干预措施: trastuzumab emtansin (Drug)
结局指标
主要结局
Pathological objective response to primary medical treatment
时间窗: At surgery
Efficacy measure after 18 weeks of preoperative treatment, starting from the start of preoperative medical treatment until the date of surgery. Outcome should be received within not more than 4 weeks post surgery
次要结局
- Overall survival(During the follow-up to 10 years)
- Disease-free survival(During the follow-up to 10 years)
- Breast cancer specific survival(During the follow-up to 10 years)
- Incidence of treatment-emergent adverse events [Safety and Tolerability](During the 18-week period of treatment and until 30 days after termination and during the follow-up period up to 10 years)
- Event-free survival(All events from date of randomization until follow-up to 10 years)
- Frequency of breast-conserving surgery(At surgery)
- Clinical/radiological objective response during neoadjuvant treatment(During the 18-week treatment period before surgery)
- Health Related Quality of life(From date of randomisation until follow-up to 5 years)
研究者
Thomas Hatschek
Sen. Consultant, MD, PhD, Assoc. professor
Karolinska University Hospital