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.
Title
- Brief Title: 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: 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)
Clinical Trial IDs
- ORG STUDY ID:
PUMA-NER-1301
- SECONDARY ID:
2012-004492-38
- SECONDARY ID:
UTN U1111-1161-1603
- NCT ID:
NCT01808573
Conditions
- HER2+ Metastatic Breast Cancer (MBC)
Interventions
Drug | Synonyms | Arms |
---|
neratinib | Nerlynx | neratinib plus capecitabine |
capecitabine | Xeloda | lapatinib plus capecitabine |
lapatinib | Tykerb, Tyverb | lapatinib plus capecitabine |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
neratinib plus capecitabine | Experimental | 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. | |
lapatinib plus capecitabine | Active Comparator | 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. | |
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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. |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | 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. |
Safety Issue: | |
Description: | 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. |
Measure: | 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. |
Safety Issue: | |
Description: | 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. |
Measure: | 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. |
Safety Issue: | |
Description: | 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. |
Measure: | 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. |
Safety Issue: | |
Description: | 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. |
Measure: | 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. |
Safety Issue: | |
Description: | 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 |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Puma Biotechnology, Inc. |
Trial Keywords
Last Updated
June 11, 2021