Neoadjuvant Trastuzumab, Pertuzumab and Tucatinib Without Chemotherapy in HER2-positive Breast Cancer: the TRAIN-4 Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
This is a single-center, phase 1b study evaluating the safety and feasibility of a neoadjuvant treatment with tucatinib, trastuzumab and pertuzumab in stage II-IIIA HER2-positive breast cancer.
详细描述
High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. However, a subset of patients with stage II-III HER2-positive breast cancer can be treated with HER2-blockade alone. These patients can potentially be totally spared from chemotherapy-associated toxicity. The proportion of patients whom can successfully be treated without chemotherapy could potentially be increased by selecting great responders using DCE-MRI and by adding tucatinib to trastuzumab and pertuzumab alone. The aim of this study is to evaluate the safety and efficacy of neoadjuvant treatment with tucatinib, trastuzumab and pertuzumab.
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
- •Signed written informed consent
- •Histologically confirmed primary invasive breast cancer
- •Stage II - IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter on DCE-MRI ≥ 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology)
- •HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy
- •Known estrogen- and progesterone-receptor expression of the invasive tumor
- •a. ER-negative or PR-negative is defined as <10% of invasive tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER and/or PR
- •WHO performance status 0-1
- •Age ≥ 18 years
- •LVEF ≥50% measured by echocardiography or MUGA
- •Eligible for neoadjuvant treatment
- •Laboratory requirements within 21 days prior to enrollment:
- •Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l);
- •Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal). Subjects with Gilbert's syndrome may have a total bilirubin ≥2.5 × the ULN range, if no evidence of biliary obstruction exists.
- •Adequate renal function: creatinine clearance >50 ml/min estimated using the Cockcroft-Gault equation or MDRD equation, or based on a 24-hour urine collection measurement.
排除标准
- •Current pregnancy or breastfeeding
- •Current or previous other malignancy unless treated without systemic therapy and more than five years ago
- •Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Use of a strong CYP3A4 or CYP2C8 inhibitor within five half-lives of the inhibitor, or used a strong CYP3A4 or CYP2C8 inducer within five days prior to first dose of study treatment
- •Known chronic liver disease
- •History of inflammatory bowel disease or bowel resection
- •Contraindications for MRI
- •Inflammatory breast cancer, cT4 and/or cN3 tumors
- •Occult breast cancer (cT0)
研究组 & 干预措施
Tucatinib + trastuzumab + pertuzumab
All patients receive neoadjuvant treatment consisting of trastuzumab, pertuzumab and tucatinib. Patients with hormone receptor positive disease receive concurrent endocrine therapy with an aromatase-inhibitor. Premenopausal women are concurrently treated with a LHRH-agonist. In case of functional tumor volume decrease of at least 65% (responders) after the first three cycles, patients continue treatment for six more cycles of the chemotherapy-free regimen. If tumor response is <65% (non-responders), patients will switch to receive six cycles paclitaxel, carboplatin, trastuzumab and pertuzumab. This is considered non-investigational treatment.
干预措施: Tucatinib (Drug)
Tucatinib + trastuzumab + pertuzumab
All patients receive neoadjuvant treatment consisting of trastuzumab, pertuzumab and tucatinib. Patients with hormone receptor positive disease receive concurrent endocrine therapy with an aromatase-inhibitor. Premenopausal women are concurrently treated with a LHRH-agonist. In case of functional tumor volume decrease of at least 65% (responders) after the first three cycles, patients continue treatment for six more cycles of the chemotherapy-free regimen. If tumor response is <65% (non-responders), patients will switch to receive six cycles paclitaxel, carboplatin, trastuzumab and pertuzumab. This is considered non-investigational treatment.
干预措施: Trastuzumab (Drug)
Tucatinib + trastuzumab + pertuzumab
All patients receive neoadjuvant treatment consisting of trastuzumab, pertuzumab and tucatinib. Patients with hormone receptor positive disease receive concurrent endocrine therapy with an aromatase-inhibitor. Premenopausal women are concurrently treated with a LHRH-agonist. In case of functional tumor volume decrease of at least 65% (responders) after the first three cycles, patients continue treatment for six more cycles of the chemotherapy-free regimen. If tumor response is <65% (non-responders), patients will switch to receive six cycles paclitaxel, carboplatin, trastuzumab and pertuzumab. This is considered non-investigational treatment.
干预措施: Pertuzumab (Drug)
结局指标
主要结局
Incidence and severity of adverse events
时间窗: an average of 8 months
Number of patients with adverse events and severity of adverse events (all grades; CTCAE v5.0) until 30 days after last study treatment administration
次要结局
- Event-free survival(3, 5, 10 years)
- Radiologic complete response(an average of 8 months)
- Pathological complete response(an average of 8 months)
- Residual Cancer Burden(an average of 8 months)
- Incidence of serious adverse events(an average of 8 months)
- Incidence of dose reductions and treatment discontinuations(an average of 8 months)
- Overall survival(3, 5, 10 years)
- Incidence of disease progression(an average of 8 months)