Randomised, Open-label Phase II Study to Compare the Safety and Efficacy of Lapatinib Plus Trastuzumab or Lapatinib Plus Capecitabine in Trastuzumab-resistant HER2-overexpressing Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Lapatinib plus trastuzumab
- Conditions
- Metastatic Breast Cancer
- Sponsor
- Berufsverband Niedergelassener Gynäkologischer Onkologen in Deutschland e.V.
- Locations
- 17
- Primary Endpoint
- 6 month progression-free-survival-rate (PFS6)
- Status
- Withdrawn
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival, tumour response and overall survival.
Detailed Description
This is an open-label, randomized, explorative phase II trial of lapatinib plus trastuzumab or lapatinib plus capecitabine in patients with HER2 overexpressing metastatic breast cancer. The trial is designed to obtain some evidence wether chemotherapy-free combined HER2-directed therapy with lapatinib and trastuzumab provides a similar efficacy as the established combination of lapatinib with capecitabine and a more favourable toxicity profile. This study will also assess the relationship between the anticipated anti-tumour activity of the treatment regimens and biological characteristics of subjects' tumour at baseline. The purpose of this study is to estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival, tumour response and overall survival. The purpose of this study ist further * to characterize the safety and tolerability of lapatinib plus trastuzumab in this population. * to identify predictors of sensitivity to lapatinib and trastuzumab therapy. and * to compare the differences in health-related quality of life (HRQL) and pain symptoms for patients by treatment assignment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed and metastatic breast cancer.
- •Hormone receptor-negative patients
- •HER2-positive tumours with 3+ intensity on IHC staining for HER2 or amplification of the HER2 gene on ISH.
- •Patients must have measurable metastatic disease by RECIST v1.1 with radiologic scans within 28 days of study registration.
- •Prior anti-HER based therapy:
- •Received at least 1 but no more than 2 prior anti-HER2 based regimens for metastatic disease.
- •Prior treatment with trastuzumab-DM1 (TDM1) is allowed (T-DM1 represents one line of anti-HER2 and one line of chemotherapy).
- •Radiological evidence of confirmed progressive disease per RECIST while receiving trastuzumab as a single agent or in combination with chemotherapy for at least 6 weeks either as first line or second line therapy, for an interval of at least 6 weeks at any time.
- •Prior treatment with Lapatinib is permitted provided that at least 6 month have elapsed since the last dose.
- •Prior chemotherapy with anthracyclines and taxanes (unless clinically contraindicated, which must have been documented).
Exclusion Criteria
- •Patients with confirmed brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Patients with treated brain metastases that are asymptomatic and have been clinically stable for 3 months will be eligible for protocol participation.
- •Hormone receptor-positive patients
- •Prior treatment with lapatinib within the last 6 months.
- •More than 2 lines of trastuzumab-based treatment for advanced disease.
- •Significant cardiovascular disease, such as
- •History of myocardial infarction, acute coronary syndromes (including unstable angina), or history of coronary angioplasty/stenting/bypass grafting within past 6 months.
- •History of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) Classes II-IV or LVEF \<50% by ECHO.
- •Severe cardiac arrhythmia requiring medication or severe conduction abnormalities.
- •Poorly controlled hypertension (resting diastolic blood pressure \>100 mmHg)
- •Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy.
Arms & Interventions
Lapatinib plus trastuzumab
Drug intervention: Lapatinib IMP, Trastuzumab on prescription. Lapatinib 1000 mg p.o. once daily for 21 days. Trastuzumab i.v. infusion 8 mg/kg loading dose; 6 mg/kg on Day 1 of each subsequent 3 weekly cycle.
Intervention: Lapatinib plus trastuzumab
Lapatinib plus Capecitabine
Drug intervention: Lapatinib and Capecitabine on prescription. Lapatinib 1250 mg p.o. once daily. Capecitabine 2000 mg/m2 p.o. in two divided doses on days 1 to 14 of a 21 day cycle.
Intervention: Lapatinib plus trastuzumab
Outcomes
Primary Outcomes
6 month progression-free-survival-rate (PFS6)
Time Frame: 6 months - from the date of randomization
The primary outcome measure for this study is: • The 6-month PFS-rate (PFS6) The 6-month PFS-rate (PFS6) will be the number of patients without disease progression or death within 6 months from the date of randomization, divided by the number of patients in the respective analysis population. For the purpose of the analysis patients who are lost to follow-up or deceased in at or before 6 months after randomization will be counted as "disease progression".
Secondary Outcomes
- Progression free survival (PFS)(the complete duration of the study (up to 72 months))