A Phase II Study Evaluating the Efficacy and Safety of Lapatinib + Vinorelbine in ErbB2 Positive Metastatic Breast Cancer Patients Pretreated With Chemotherapy or Hormonal Treatment in Combination With Lapatinib for Metastatic Disease
The objective of this phase II study is to gain first information on the efficacy (PFS, ORR
and OS) and safety of lapatinib plus vinorelbine in patients with HER2 positive breast
cancer pretreated with a combination therapy (chemotherapy, hormonal therapy) including
lapatinib for metastatic disease.
The sample size is not based on statistical consideration. Thirty 30 patients are considered
appropriate for a phase II study to gain first information on the efficacy and safety of the
study treatment in the study indication.
Only descriptive statistical methods will be used to summarize the study results.
Kaplan-Meier estimates will be calculated for PFS and OS. Median PFS and OS time and
corresponding two sided 95% confidence intervals will be provided.
Categorical endpoints will be summarized in frequency tables and 95% confidence intervals
will be calculated for the objective response rate (ORR) using RECIST.
All safety variables will be summarized descriptively The incidence of adverse events will
be summarized by MedDRA terms in a descriptive manner.
The progression free survival time (PFS) is the primary efficacy endpoint of the study.
Secondary outcomes are overall survival (OS) and objective response rates (ORR) using
Safety outcomes are adverse events, safety laboratory data, physical examinations, vital
signs, LVEF, ECG data and ECOG performance status
The objective response rate is the rate of subjects with complete response (CR) or partial
The time to progression or death is defined as the time from study entry until the first
observation of disease progression or death due to any cause (whichever occurred earlier).
Only those death will be considered, which occurs within 84 days of the last tumor
assessment or study entry (whichever is later).
If a patient has no progression before a clinical cut-off or the death date is beyond the
above-mentioned time interval after last tumor assessment, time to progression/death is
censored on the date of last tumor assessment or study entry (in case of no post-baseline
Overall survival will be calculated from study entry until death. For patients lost to
follow-up, data will be censored at the time the patient was last determined to be alive.
As efficacy data of vinorelbine plus lapatinib are not available so far and the current
protocol is applied as 2nd or 3rd line therapy for metastatic disease an ORR from 30-40% and
a median PFS from 4-6 months is expected.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progressive Free Survival
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Istvan Lang, MD
National Institute of Oncology Rath Gyorgy u. 7-9. 1122 Budapest
Austria: Agency for Health and Food Safety