Neratinib Dose Escalation Regimen for HER2 Positive Early Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- Primary Endpoint
研究概览
简要总结
This is a prospective study on the prevention of Neratinib-related diarrhea in a Chinese population, exploring the best options for reducing the incidence of neratinib-related diarrhea through either pharmacologic intervention (prophylactic antidiarrheal therapy) or non-pharmacologic intervention (dose escalation program).
详细描述
This is A prospective, randomized, single-center clinical trial, divided into 3 groups (experimental group: group A and group B, control group: group C), planned sixty patients were enrolled, with 20 patients in each group.
Experimental group: Group A (n=20) and group B (n=20) were given neratinib dose escalation regimen foranti-HER2 adjuvant therapy.In group A, the dose of neratinib climbed up to 240mg within 2 weeks, and in group B, the dose climbed up to 240mg within 4 weeks.
Control group: Group C (n=20) was given 240mg neratinib initially, but prophylactic loperamide antidiarrhea treatment was given at the same time within 2 months.
Diarrhea caused by neratinib often occurred within 1-2 months of initial treatment, so small dose of neratinib was used in both group A and group B at the time of initial treatment.
The incidence and severity of neratinib-related diarrhea in the three groups were observed, and DFS and other neratinib-related adverse events were followed up for a long time. The study is to evaluate the safety and efficacy of neratinib dose escalation regimen and conventional dose combined with loperamide regimen in enhanced anti-HER2 adjuvant therapy for early HER2-positive 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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 75 year-old women；
- •ECOG score: 0-1；
- •HER2 positive breast cancer diagnosed histologically is defined as HER2 (3+) by immunohistochemistry or HER2 (2+) with positive FISH test；
- •Postoperative pathological stage ⅱ → ⅲ, or initial stage (before neoadjuvant therapy) ⅱ → ⅲ, radiographic assessment showed no metastasis;
- •Complete 1 year of anti-HER2 therapy with trastuzumab, prior use of pertuzumab neoadjuvant + adjuvant therapy or T-DM1 adjuvant therapy is permitted;
- •No major organ dysfunction, contraception;
- •The patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the Informed Consent Form.
排除标准
- •Patients who are allergic to the study drug, cannot take the drug orally, or refuse the medication regimen;
- •Prior treatment with TKI anti-HER-2 drugs (e.g. Lapatinib, Pyrotinib, etc.);
- •Patients were enrolled in other studies or stopped taking other drugs within 4 weeks;
- •Patients with serious dysfunction of important organs (heart, liver and kidney);
- •Patients with other malignancies, other than cured non-melanoma skin cancer, carcinoma in situ of the cervix and other tumors that have been cured for at least 5 years;
- •In pregnancy, lactation patients;
- •In the active stage of other acute or chronic infectious diseases;
- •The patients have uncontrollable mental illness;
- •There is a known history of human immunodeficiency virus;
- •There are other circumstances in which the investigator suggested that the patient should not participate in the study.
研究组 & 干预措施
Neratinib escalation 2 weeks（group A）
Neratinib: 120mg/ day for days 1-7, 160mg/ day for days 8-14, and then 240mg/ day to complete 1-year treatment, or to tumor recurrence and metastasis, new breast cancer, or unacceptable adverse reactions within 1 year.
干预措施: Neratinib (Drug)
Neratinib escalation 4 weeks（group B）
Neratinib: 160mg/ day for days 1-14, 200mg/ day for days 15-28, and then 240mg/ day for 1 year, or to tumor recurrence and metastasis, new breast cancer, or unacceptable adverse reactions within 1 year.
干预措施: Neratinib (Drug)
Neratinib standard dose control （group C）
Neratinib: 240mg/ day for 1 year, or to tumor recurrence and metastasis, new breast cancer or unacceptable adverse reactions within 1 year.
Loperamide prophylaxis: 4mg three times daily on days 1-14 and 4mg twice daily on days 15-56, followed by as needed, not exceeding 16mg/ day.
干预措施: Neratinib (Drug)
结局指标
主要结局
Primary Endpoint
时间窗: up to 3 year after the last patient enrolled
Incidence of grade ≥3 diarrhea in patients with her2-positive early breast cancer treated with neratinib dose escalation versus neratinib conventional dose combined with loperamide
次要结局
- Secondary Endpoint(up to 3 year after the last patient enrolled)
研究者
Peng Yuan
Chief of VIP department
Chinese Academy of Medical Sciences