Conditions: Breast Cancer
Keywords: Solid Tumor erbB2+ Breast Cancer Prior trastuzumab Metastatic Neratinib HKI-272 Nerlynx HER2 PB-272
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 105
Healthy volunteers: no

Brief summary:
This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.

In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.

Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.

In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.

Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.

The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.

The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.

The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.

Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.

Detailed description:

Arms:
arm 1: Neratinib 160 mg and Capecitabine 1500 mg/m\^2 arm 2: Neratinib 240 mg and Capecitabine 1500 mg/m\^2 arm 3: Neratinib 240 mg and Capecitabine 2000 mg/m\^2 arm 4: Neratinib 200 mg and Capecitabine 2000 mg/m\^2 arm 5: Neratinib 160 mg and Capecitabine 2000 mg/m\^2 arm 6: Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib arm 7: Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib

Interventions: intervention 1: Neratinib intervention 2: Capecitabine
Intervention descriptions: intervention 1: Neratinib orally once daily continually intervention 2: Capecitabine orally on days 1-14 of each 21 day cycle

Protocol document: