An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 563
- 试验地点
- 57
- 主要终点
- Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
研究概览
简要总结
An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients with Early-Stage HER2+ Breast Cancer Treated with Neratinib and Loperamide or other prophylactic measures.
详细描述
This is an open-label, Phase 2 study that will investigate the incidence and severity of diarrhea in early-stage HER2+ breast cancer patients receiving neratinib with loperamide, alone and in combination with an anti-inflammatory treatment or a bile acid sequestrant treatment, or neratinib dose escalation, who have previously undergone a course of trastuzumab therapy in the adjuvant setting.
Patients will receive:
- Neratinib 240 mg orally once daily with food for thirteen 28-day cycles.
- Loperamide daily for two 28-day cycles and then as needed.
- Amendment 3, an anti-inflammatory treatment for one cycle and loperamide to be administered daily for two 28-day cycles and then as needed. Closed to enrollment.
- Amendment 4, colestipol for one cycle and loperamide to be administered one cycle and then as needed. Closed to enrollment.
- Amendment 5, colestipol for one cycle and loperamide as needed. Closed to enrollment.
- Amendment 6/6.1, 120 mg neratinib for Week 1 (C1D1-C1D7), followed by 160 mg neratinib for Week 2 (C1D8-C1D14), followed by 240 mg neratinib for Week 3 and thereafter (C1D15 to end of treatment). Loperamide as needed. Closed to enrollment.
- Amendment 7/7.1, 160 mg neratinib for the first 2 weeks (C1D1 - C1D14), followed by 200 mg neratinib for the next 2 weeks (C1D15 - C1D28), followed by 240 mg neratinib thereafter (C2D1 to end of treatment). Loperamide as needed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age ≥18; male or female
- •Early breast cancer (stage I-3c)
- •Documented HER2+ tumor: HER2 immunohistochemistry (IHC) 3+ or ISH+
- •Prior course of adjuvant trastuzumab given >2 weeks and ≤1 year from enrollment
- •No evidence of local/regional recurrence or metastatic disease
- •Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
- •Male patients with female partners of childbearing potential must agree and commit to use a condom and women of childbearing potential must not be pregnant and must agree and commit to the use of a highly effective non-hormonal method of contraception
- •Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or ECHO
排除标准
- •Major surgery < 30 days
- •Chemotherapy, investigational agents, other cancer therapy (except hormonal therapy) < 14 days
- •Corrected QT Interval (QTc) >0.450 seconds (males) or >0.470 (females) or other active cardiac disease
- •Significant chronic GI disorder with diarrhea as a major symptom
- •Active, unresolved infections
- •Currently pregnant or breast-feeding
研究组 & 干预措施
Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.
干预措施: Neratinib (Drug)
Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Loperamide daily for two 28-day cycles and then as needed.
干预措施: Loperamide (Drug)
Budesonide and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.
干预措施: Neratinib (Drug)
Budesonide and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.
干预措施: Loperamide (Drug)
Budesonide and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Anti-inflammatory treatment for 1 cycle and Loperamide to be administered daily for two 28-day cycles and then as needed, thereafter.
干预措施: Budesonide (Drug)
Colestipol and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.
干预措施: Neratinib (Drug)
Colestipol and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.
干预措施: Loperamide (Drug)
Colestipol and Loperamide
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered 1 cycle and then as needed, thereafter.
干预措施: Colestipol (Drug)
Colestipol with Loperamide as needed
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
干预措施: Neratinib (Drug)
Colestipol with Loperamide as needed
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
干预措施: Loperamide (Drug)
Colestipol with Loperamide as needed
240 mg Neratinib orally once daily with food for thirteen 28-day cycles. Colestipol for 1 cycle and loperamide to be administered as needed.
干预措施: Colestipol (Drug)
Neratinib Dose Escalation 1
120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.
干预措施: Neratinib (Drug)
Neratinib Dose Escalation 1
120 mg Neratinib for Week 1, followed by 160 mg Neratinib starting for Week 2, followed by 240 mg Neratinib starting at Week 3 and thereafter (C1D15 to End of Treatment). Loperamide administered as needed.
干预措施: Loperamide (Drug)
Neratinib Dose Escalation 2
160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.
干预措施: Neratinib (Drug)
Neratinib Dose Escalation 2
160 mg neratinib for the first 2 weeks, followed by 200 mg neratinib for the next 2 weeks, followed by 240 mg neratinib thereafter (C2D1 to End of treatment. Loperamide will be administered on an as-needed basis only.
干预措施: Loperamide (Drug)
结局指标
主要结局
Percentage of Patients With Grade 3 or Higher Diarrhea, According to NCI CTCAE v4.0.
时间窗: From first dose of investigational product through 28 days after last dose, up to 15.5 months.
The primary objective of this study is to characterize the percentage of patients with Grade 3 or higher diarrhea in patients with early-stage HER2 overexpressed/amplified (HER2+) breast cancer treated with neratinib when administered with intensive loperamide prophylaxis, after prior treatment with trastuzumab. Grade 3: Increase of \>=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death.
次要结局
- Percentage of Patients With Serious Adverse Events and Other Adverse Events of Special Interest(From first dose of investigational product through 28 days after last dose, up to 15.5 months.)
- Percentage of Patients With Diarrhea by Grade, According to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), Version 4.0.(From first dose of investigational product through 28 days after last dose, up to 15.5 months.)