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.