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A Multicenter, Open-Label, Phase II Study of Lapatinib in Combination With Vinorelbine in Subjects With ErbB2 Amplified Recurrent and Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling

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Trial Information

A Multicenter, Open-Label, Phase II Study of Lapatinib in Combination With Vinorelbine in Subjects With ErbB2 Amplified Recurrent and Metastatic Breast Cancer

This is a Multicenter, Open-Label, Phase II Study of lapatinib in Combination with
Vinorelbine in women with documented evidence of HER2/neu positive breast cancer which is
metastatic or recurrent and with or without prior chemotherapy or anti-HER2/neu targeted
therapy in the metastatic and relaps setting.

Patients will receive 1250mg lapatinib once a day and vinorelbine 25mg/sqm IV Day 1and Day
8, every 3 week for 24 weeks. The study treatment will continue until patients experience
disease progression or unacceptable toxicity. The primary objective of the study is the
objective response rate (ORR, defined as CR + PR) and toxicity. Secondary objectives include
DFS, duration of response.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the breast.

- Patients must be > 18 years of age

- Metastatic breast cancer (stage IV) at primary diagnosis or at relapse after curative
intent therapy.

- Laboratory confirmed HER2/neu overexpressing and/or amplified disease in the invasive
component of the primary or metastatic lesion

- Patients must have evidence of metastatic disease, but measurable disease is not

- The patients may have received or not prior treatment with chemotherapeutic agents
including taxanes, trastuzumab or anthracycline in the adjuvant or metastatic setting
is permitted.

- Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are
permitted provided that at least 4 weeks have elapsed since the last fraction of
radiation therapy and all treatment related adverse events are < grade 1 at the time
of enrollment.

- Prior radiation to a solitary metastatic lesion is permitted provided that
progression post radiation has been documented.

- Patients must have life expectancy > 3 months.

- ECOG performance status 0, 1 or 2 (see Appendix II).

- Patients must have normal organ and marrow function measured within 14 days prior to
enrollment as defined Table 1.

- Left ventricular ejection fraction > 50% as demonstrated by MUGA scan/echocardiogram
within 4 weeks prior to enrollment.

- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to
enrollment and must use an acceptable method of contraception for the duration of the

Female patients who are lactating should discontinue nursing prior to the first dose of
investigational product and should refrain from nursing throughout the treatment period
and for 14 days following the last dose of investigational product.

- The patient must sign the consent form prior to enrollment.

- Patients must be accessible for treatment and follow-up.

Exclusion Criteria:

- Patients with a history of other malignancies, except: adequately treated DCIS,
adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the
cervix, or other solid tumours (non-breast) curatively treated with no evidence of
disease for > 5 years.

- Patients receiving ongoing anticancer treatment or other investigational anti-cancer
agents for breast cancer or patients who have used an investigational drug within 30
days or 5 half-lives (if known), whichever is longer, preceding the date of

- Patients with symptomatic CNS metastases (including leptomeningeal involvement).

- Patients with only bone metastasis.

- Patients with serious cardiac illness or condition including, but not limited to:

history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF<50%)
high risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block,
supraventricular arrhythmias which are not adequately rate-controlled) unstable angina
pectoris requiring anti-anginal medication clinically significant valvular heart disease
evidence of transmural infarction on ECG inadequately controlled hypertension (systolic
blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg).

New York Heart Association (NYHA) Class III or IV functional status (see Appendix X)

- Patients who have received vinorelbine as a prior therapy in the metastatic and
recurrent setting.

- Patients with serious illness or medical condition which would not permit the patient
to be managed according to the protocol including, but not limited to:

- History of significant neurologic or psychiatric disorder which would impair the
ability to obtain consent or limit compliance with study requirements.

- Active uncontrolled infection. Serious or non-healing wound, ulcer, or bone fracture.

- Patients with GI tract disease resulting in an inability to take oral medication such
as but not limited to malabsorption syndrome, a requirement for IV alimentation,
prior surgical procedures affecting absorption (for example resection of stomach or
small bowel) or uncontrolled inflammatory GI disease (e.g. Crohn's, ulcerative

- Patients receiving CYP3A4 inhibitors or inducers are not eligible unless it has been
> 7 and > 14 days, respectively since the last dose of medication before the start of
protocol treatment (see Appendix IX). For amiodarone in particular, dosing is
prohibited for at least 6 months prior to the start of protocol treatment.

- Patients with history of allergic or hypersensitivity reactions to any study drug or
their excipients or with a history of allergic reactions attributed to compounds with
similar chemical composition to any of the study drugs.

- Pregnant or lactation women

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants (Par.) With Clinical Benefit (CB) at Week 12 and Week 24

Outcome Description:

Par. with CB are defined as those with complete response (CR), partial response (PR), or stable disease (SD) for >=12 or 24 weeks. Per Response Evaluation Criteria In Solid Tumors (RECIST), Version 1.1, CR is defined as the disappearance of all target lesions, PR is defined as a >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD, and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as a reference the smallest sum LD since the treatment started.

Outcome Time Frame:

Week 12 and Week 24

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Turkey: Ministry of Health

Study ID:




Start Date:

April 2009

Completion Date:

March 2012

Related Keywords:

  • Cancer
  • lapatinib
  • breast cancer
  • Breast Neoplasms