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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)

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ClinicalTrials.gov Identifier: NCT01808573
Recruitment Status : Active, not recruiting
First Posted : March 11, 2013
Last Update Posted : September 26, 2018
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
Last Update Posted Date September 26, 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: September 24, 2018)
  • 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 and Serious Adverse Events) [ 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
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 Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Population pharmacokinetics [ Time Frame: 1 month following enrollment ]
Variability of neratinib concentration when administered in combination with capecitabine among individuals in the target population.
Original 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.
 
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
    Other Name: Nerlynx
  • Drug: capecitabine
    Other Name: Xeloda
  • Drug: lapatinib
    Other Names:
    • Tykerb
    • Tyverb
Study Arms
  • 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 * 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 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
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
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
Study Director: Clinical Development Senior Vice President Puma Biotechnology, Inc.
PRS Account Puma Biotechnology, Inc.
Verification Date September 2018

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