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)

Tracking Information
First Submitted Date ICMJE	March 4, 2013
First Posted Date ICMJE	March 11, 2013
Last Update Posted Date	March 9, 2018
Actual Study Start Date ICMJE	March 29, 2013
Estimated Primary Completion Date	February 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 7, 2013)	Independently assessed Progression Free Survival [ Time Frame: Estimated 10 months ]; Overall Survival [ Time Frame: Estimated 28 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01808573 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 7, 2013)	Investigator Assessed Progression Free Survival [ Time Frame: Estimated 10 months ]; Objective Response Rate (ORR) [ Time Frame: Estimated 10 months ]; Clinical Benefit Rate (CBR) [ Time Frame: 24 weeks ]CBR is defined as Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 24 weeks.; Duration of Response (DOR) [ Time Frame: Estimated 10 months ]; Time to intervention for symptomatic metastatic central nervous system disease [ Time Frame: Estimated 10 months ]; Safety (Adverse Events [AEs] and Serious Adverse Events [SAEs]) [ Time Frame: From consent through 30 days following treatment completion (estimated 11 months) ]; Health Outcomes Assessments [ Time Frame: Estimated 10 months ]Validated Quality of Life Questionnaires; EORTC QLQ-C30, EORTC QLQ-BR23, and EQ-5D-5L
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE; (submitted: March 7, 2013)	Population pharmacokinetics [ Time Frame: 1 month following enrollment ]; To assess the variability of neratinib concentration when administered in combination with capecitabine among individuals in the target population.
Original Other Outcome Measures ICMJE	Same as current
Descriptive Information
Brief Title ICMJE	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
Official Title ICMJE	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
Brief Summary	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.
Detailed 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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HER2+ Metastatic Breast Cancer (MBC)
Intervention ICMJE	Drug: neratinib 240 mg orally, once daily with food, continuously in 21 day cycles; Drug: 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. Other Name: Xeloda; Drug: lapatinib 1250 mg orally, once daily, continuously in 21 day cycles Other Names: Tykerb Tyverb; Drug: 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. Other Name: Xeloda
Study Arms	Experimental: neratinib plus capecitabine Interventions: Drug: neratinib Drug: capecitabine; Active Comparator: lapatinib plus capecitabine Interventions: Drug: lapatinib Drug: capecitabine
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: October 9, 2017)	621
Original Estimated Enrollment ICMJE; (submitted: March 7, 2013)	600
Estimated Study Completion Date	February 2019
Estimated Primary Completion Date	February 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Aged ≥18 years at signing of informed consent.; Histologically confirmed MBC, current stage IV.; Documented HER2 overexpression or gene-amplified tumor (immunohistochemistry [IHC] 3+ or IHC 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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, Portugal, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT01808573
Other Study ID Numbers ICMJE	PUMA-NER-1301; 2012-004492-38 ( EudraCT Number ); UTN U1111-1161-1603 ( Other Identifier: WHO )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	Puma Biotechnology, Inc.
Study Sponsor ICMJE	Puma Biotechnology, Inc.
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Puma Biotechnology, Inc.
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP