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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.
Full 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
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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:
Prior chemotherapy with anthracyclines and taxanes (unless clinically contraindicated, which must have been documented).
Patients must have the following laboratory values:
Normal cardiac function with a left ventricular ejection fraction of at least 50% (as assessed by quantitative echocardiogram)
ECOG performance status 0-1
Age ≥ 18 years
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had hysterectomy, a bilateral oophorectomy, bilateral tubular ligation or is post-menopausal (total cessation of menses for ≥ 1 year; if the patient is of childbearing potential, she must have a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.
Written informed consent prior to admission to this study.
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
QTc prolongation defined as a QTc interval > 460 msec or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate < 50 beats/min)
Subjects who have current active hepatic or biliary disease or severe hepatic impairment (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Malabsorption syndrome or other condition that would interfere with enteral absorption
Hypersensitivity to trastuzumab, murine proteins or to any of the excipients.
Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
History of severe and unexpected reactions to fluoropyrimidine therapy.
Hypersensitivity to capecitabine or to any of the excipients or fluorouracil.
Known dihydropyrimidine dehydrogenase (DPD) deficiency.
Severe leucopenia, neutropenia or thrombocytopenia.
Severe renal impairment (creatinine clearance < 40 ml/min.).
Treatment with sorivudine or its chemically related analogues, such as brivudine.
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
Contraindications to any of the medicinal products in the combination regimen.
Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol.
Patients accommodated in a closed institution by authority or court order.
Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry.
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Data sourced from clinicaltrials.gov
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