A Study of Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in Patients With HER2+ Metastatic Breast Cancer Who Have Received Two or More Prior HER2 Directed Regimens in the Metastatic Setting (NALA)

Puma Biotechnology

Status and phase: Completed; Phase 3

Conditions: HER2+ Metastatic Breast Cancer (MBC)

Treatments: Drug: neratinib; Drug: capecitabine; Drug: lapatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01808573

2012-004492-38 (EudraCT Number)

UTN U1111-1161-1603 (Other Identifier)

PUMA-NER-1301

Details and patient eligibility

About

This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting.

Full description

This is a randomized, multi-center, multinational, open-label, active-controlled, parallel design study of the combination of neratinib plus capecitabine versus the combination of lapatinib plus capecitabine in HER2+ MBC patients who have received two or more prior HER2 directed regimens in the metastatic setting. Patients will be randomized in a 1:1 ratio to one of the following treatment arms:

• Arm A: neratinib (240 mg once daily) + capecitabine (1500 mg/m^2 daily, 750 mg/m^2 twice daily [BID])
• Arm B: lapatinib (1250 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)

Patients will receive either neratinib plus capecitabine combination or lapatinib plus capecitabine combination until the occurrence of death, disease progression, unacceptable toxicity, or other specified withdrawal criterion.

Enrollment: 621 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Aged ≥18 years at signing of informed consent.
• Histologically confirmed MBC, current stage IV.
• Documented HER2 overexpression or gene-amplified tumor immunohistochemistry 3+ or 2+, with confirmatory fluorescence in situ hybridization (FISH) +.
• Prior treatment with at least two (2) HER2-directed regimens for metastatic breast cancer.

Exclusion criteria

• Received previous therapy with capecitabine, neratinib, lapatinib, or any other HER2 directed tyrosine kinase inhibitor.

Note: There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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621 participants in 2 patient groups

neratinib plus capecitabine

Experimental group

Description:

neratinib 240 mg orally, once daily with food, continuously in 21 day cycles, and capecitabine 1500 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.

Treatment:

Drug: capecitabine

Drug: neratinib

lapatinib plus capecitabine

Active Comparator group

Description:

lapatinib 1250 mg orally, once daily, continuously in 21 day cycles, and capecitabine 2000 mg/m\^2 daily in 2 evenly divided doses, orally with water within 30 minutes after a meal, taken on days 1 to 14 of each 21 day cycle.

Treatment:

Drug: lapatinib

Drug: capecitabine