Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01808573
Recruitment Status : Completed
First Posted : March 11, 2013
Results First Posted : December 11, 2019
Last Update Posted : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Tracking Information
First Submitted Date  ICMJE March 4, 2013
First Posted Date  ICMJE March 11, 2013
Results First Submitted Date  ICMJE September 27, 2019
Results First Posted Date  ICMJE December 11, 2019
Last Update Posted Date March 18, 2020
Actual Study Start Date  ICMJE March 29, 2013
Actual Primary Completion Date September 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2020)
  • Centrally Assessed Progression Free Survival [ Time Frame: From randomization date to recurrence, progression or death, assessed up to 38 months. The result is based on primary analysis data cut. ]
    Progression Free Survival (PFS), Measured in Months, for Randomized Subjects of the Central Assessment. The time interval from the date of randomization until the first date on which recurrence, progression (per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1), or death due to any cause, is documented. For subjects without recurrence, progression or death, it is censored at the last valid tumor assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 24 months.
  • Overall Survival [ Time Frame: From randomization date to death, assessed up to 59 months.The result is based on primary analysis data cut. ]
    Overall survival (OS) is defined as the time from randomization to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. Here, the time to event was reported as the restricted mean survival time. The restricted mean survival time was defined as the area under the curve of the survival function up to 48 months.
Original 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2020)
  • Intervention for Symptomatic Metastatic Central Nervous System Disease [ Time Frame: From randomization date to first intervention for symptomatic metastatic CNS disease, assessed up to 59 months.The result is based on primary analysis data cut. ]
    Intervention for symptomatic metastatic central nervous system disease is defined as the time from randomization to the first start date of an intervention for symptomatic metastatic CNS disease. Subjects that do not have an intervention for symptomatic metastatic CNS and do not die will be censored at the last date known alive on or prior to the data cutoff. Deaths are treated as competing events. Percentage of participants with intervention for CNS, estimated by cumulative incidence methods. Cumulative incidence methods are the standard way to estimate incidence of an endpoint in the presence of competing risks and censoring.
  • Objective Response Rate (ORR) - Central Assessment (ITT Population With Measurable Disease at Screening) [ Time Frame: From randomization date to first confirmed Complete or Partial Response, whichever came earlier, up to 42 months.The result is based on primary analysis data cut. ]
    Objective response rate is defined as the percentage of participants demonstrating an objective response during the study. Objective response includes confirmed complete responses (CR) and partial responses (PR) as defined in the RECIST criteria included in the study protocol. The ORR is for Central Assessment for subjects that had measurable disease at screening. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
  • Clinical Benefit Rate (CBR) - Central Assessment (ITT Population With Measurable Disease at Screening) [ Time Frame: From randomization date to either first confirmed CR or PR or Stable Disease, whichever came earlier, up to 42 months.The result is based on primary analysis data cut. ]
    Clinical benefit rate is the percentage of participants who achieve overall tumor response (confirmed CR or PR) or stable disease (SD) lasting for at least 24 weeks from randomization. The CBR was for Central Assessment for subjects who had Measurable Disease at Screening.
  • Duration of Response (DOR) - Central Assessment (Population That Had a Response With Measurable Disease at Screening) [ Time Frame: From start date of response after randomization to first PD, up to 33 months.The result is based on primary analysis data cut. ]
    The Duration of Response (DOR) is for Central Assessment for the Population that Had a Response with Measurable Disease at Screening. Duration of response is measured from the time at which measurement criteria are first met for CR or PR (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented, taking as a reference for PD the smallest measurements recorded since enrollment, per RECIST v1.1. This value is censored at the last valid tumor assessment if PD or death has not been documented.
  • Percentage of Participants With Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) [ Time Frame: From first dose through last dose + 28 days, up to 41 months. The result is based on final data cut. ]
    Adverse Events to be measured are Treatment-Emergent and Serious AEs that occurred on or after first dose of investigational product and up to 28 days after the last dose
Original 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (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.
 
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 (NALA)
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  ICMJE 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
    Other Name: Nerlynx
  • Drug: capecitabine
    Other Name: Xeloda
  • Drug: lapatinib
    Other Names:
    • Tykerb
    • Tyverb
Study Arms  ICMJE
  • Experimental: neratinib plus capecitabine
    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.
    Interventions:
    • Drug: neratinib
    • Drug: capecitabine
  • Active Comparator: lapatinib plus capecitabine
    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.
    Interventions:
    • Drug: capecitabine
    • Drug: lapatinib
Publications * Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N, Palacova M, Trudeau ME, Mattson J, Yap YS, Hou MF, De Laurentiis M, Yeh YM, Chang HT, Yau T, Wildiers H, Haley B, Fagnani D, Lu YS, Crown J, Lin J, Takahashi M, Takano T, Yamaguchi M, Fujii T, Yao B, Bebchuk J, Keyvanjah K, Bryce R, Brufsky A; NALA Investigators. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial. J Clin Oncol. 2020 Jul 17:JCO2000147. doi: 10.1200/JCO.20.00147. [Epub ahead of print]

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: October 9, 2017)
621
Original Estimated Enrollment  ICMJE
 (submitted: March 7, 2013)
600
Actual Study Completion Date  ICMJE December 9, 2019
Actual Primary Completion Date September 28, 2018   (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 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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  ICMJE Not Provided
Responsible Party Puma Biotechnology, Inc.
Study Sponsor  ICMJE Puma Biotechnology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Development Chief Medical and Scientific Officer Puma Biotechnology, Inc.
PRS Account Puma Biotechnology, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP