The investigators address the clinical efficacy of continuing lapatinib treatment combined with vinorelbine after the progression of both trastuzumab and lapatinib treatment compared with vinorelbine alone in HER2 positive metastatic breast cancer patients.
This study is a multicenter, randomized, open label, phase II study. Patients will be randomized to either lapatinib plus vinorelbine (LV) arm or vinorelbine alone (V) arm, if they are satisfied by inclusion and exclusion criteria. The stratification factors are followings: 1) visceral metastasis vs. others, 2) previous response to lapatinib treatment, complete response(CR)+partial response(PR) vs. stable disease(SD)≥ 12wks. Patients in LV arm will receive daily lapatinib 1,000mg with vinorelbine 20mg/m2 day1 and day 8. Patients in V arm will receive vinorelbine 30mg/m2 day 1 and day 8. Treatment repeats every 21 days unless there is any evidence of disease progression or unacceptable toxicity or noncompliance by patient with protocol requirements. Response will be documented by physical examination, chest or abdomen CT prior to treatment as a baseline, and every 2 cycles (window period ± 1 week) after a start of treatment and at 18 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
lapatinib 1000mg, once daily
Vinorelbine 20mg/m2, D1 and D8, every 3 weeks
National Cancer Center
Goyang-si, Gyeonggi-do, South Korea
RECRUITINGProgression free survival rate at 18 weeks
The PFS rate at 18 weeks will be calculated as the ratio of patients on the study to Intent to treat (ITT) population at the time point of 18 weeks from the initiation of study treatment. The ITT population will consist of all patients who are randomized.
Time frame: The time point of 18 weeks from the initiation of study treatment.
Progression free survival (PFS)
The secondary objective of this study is to estimate the PFS and OS in both arms and median PFS and OS will be estimated by Kaplan-Meier estimates and compared by log-rank test. Response rate will be calculated as the proportion of patients with a complete or partial tumor response among ITT population. Chi-square test will be used to PFS rate and compare response rates between the two arms (categorical variables).
Time frame: From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months
Overall survival (OS)
The secondary objective of this study is to estimate the OS in both arms will be estimated by Kaplan-Meier estimates and compared by log-rank test.
Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months
toxicity
All toxicities during treatment will be recorded according to NCI-common toxicity criteria for adverse effects version 4.0.
Time frame: From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months
response rate
Objective response mean complete response and partial response according to Response evaluation criteria in solid tumors v 1.1 and response will be assessed every 6 weeks.
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Time frame: From date of randomization until the date of first documented progression, withdrawal from the study, or date of death from any cause, whichever came first, assessed up to 36 months