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A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination With Vinorelbine or Capecitabine in Women With ErbB2 Overexpressing Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)

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Trial Information

A Phase II, Randomised, Multi-Centre Study Evaluating Lapatinib in Combination With Vinorelbine or Capecitabine in Women With ErbB2 Overexpressing Metastatic Breast Cancer

Approximately 105 subjects will be enrolled in the study and randomized 2:1 to one of the
following regimens Arm A (n=70): Lapatinib 1250 mg orally once daily continuously plus
Vinorelbine 20mg/m2 intravenously (IV) on day 1 and 8, every third week, or Arm B (n=35):
Lapatinib 1250 mg orally once daily (QD) continuously plus Capecitabine 2000 mg/m2/day
orally in 2 doses 12 hours apart on days 1-14 every third week. Randomization will be
stratified according to the following variables: 1) Prior receipt of therapy for metastatic
breast cancer (Yes or No), and 2) Site of metastatic disease (Visceral/Soft tissue or
Bone-only). Subjects will receive randomized study treatment until disease progression or
discontinuation of study treatment due to unacceptable toxicity, withdrawal of consent, lost
to follow up, or death. All subjects who discontinue study treatment without documented
progression will continue to be followed for progression according to protocol-schedule
until new anti-cancer therapy is initiated and/or progression or death is documented.
Survival data will be collected for all subjects to ensure a minimum of 18 months survival
data. This study will include a safety run-in phase for approximately the first 30 subjects
(20 randomized to lapatinib and vinorelbine; 10 to lapatinib and capecitabine).

Inclusion Criteria

Inclusion Criteria :

- Signed informed consent prior to registration.

- Considered by the investigator to have a life expectancy of ≥12 weeks.

- Subjects must be female and have histologically - confirmed invasive breast cancer
with Stage IV disease at primary diagnosis or at relapse after curative - intent

- Documented overexpression of ErbB2

- Subjects should have progressive disease following prior therapy which may include
anthracyclines, taxanes, and trastuzumab.

- Females aged ≥18 years

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.

- Subjects must have adequate organ and marrow function

- Subjects must have a cardiac ejection fraction of at least 50% and within the
institutional range of normal.

- Radiotherapy prior to initiation of study medication is allowed to a limited area ( e
. g . , palliative therapy ) , if it is not the sole site of disease.

- Subjects with stable central nervous system (CNS) metastases are permitted.

- Subject must be free of gastrointestinal diseases or any other conditions that impede
swallowing, retaining, and absorption of oral medications.

- Bisphosphonate therapy for bone metastases is allowed; however, treatment must be
initiated prior to the first dose of study medication. Prophylactic use of
bisphosphonates in subjects without bone disease, except for the treatment of
osteoporosis, is not permitted.

Exclusion Criteria:

- Subjects taking prohibited medications are not eligible for the study.

- Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this

- Prior therapy with more than one chemotherapeutic regimen for metastatic breast

- Concurrent anticancer or concomitant radiotherapy treatment.

- History of uncontrolled or symptomatic angina; history of arrhythmias requiring
medications ; clinically significant myocardial infarction < 6 months from study
entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below
the institutional normal limit; or any other cardiac condition, which in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the

- Have current active hepatic or biliary disease (with exception of patients with
Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
disease per investigator assessment).

- Use of an investigational drug within 30 days or 5 half - lives, whichever is longer,
preceding the first dose of investigational treatment, or, concurrent treatment with
an investigational agent or participation in another clinical trial involving
investigational agents.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the agents used in this study or their excipients that
in the opinion of the investigator or GSK Medical Monitor contraindicates their

- Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).

- Known history of uncontrolled inter - current illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social
situations that would limit compliance with study requirements.

- Concurrent disease or condition that would make the subject inappropriate for study
participation , or any serious medical disorder that would interfere with the
subject's safety.

- Pregnant or lactating females at any time during the study (due to the potential
teratogenic or abortifacient effects of lapatinib and breastfeeding).

- Subjects with diseases affecting gastrointestinal function resulting in an inability
to take oral medication , including ; malabsorption syndrome, disease significantly
affecting gastrointestinal function , or resection of the stomach , small bowel , or
colon. Subjects with inflammatory bowel disease or ulcerative colitis are also

- Peripheral neuropathy of Grade 2 or greater.

- Unresolved or unstable, serious toxicity from prior administration of another
investigational drug and / or of prior cancer treatment.

- Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS) in the Randomized Phase

Outcome Description:

PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. PD is defined as at least a 20 % increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >=1 new lesion.

Outcome Time Frame:

From randomization until disease progression, death, or discontinuation from the study (average of 27 study weeks)

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Spain: Agencia Española del Medicamento y Productos Sanitarios

Study ID:




Start Date:

November 2009

Completion Date:

August 2014

Related Keywords:

  • Cancer
  • Neoplasms, Breast