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

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.

Inclusion criteria

• 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

Exclusion criteria

• 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