Know Cancer

forgot password

Randomized Phase II Study of Lapatinib Plus Vinorelbine Versus Vinorelbine in Patients With HER2 Positive Metastatic Breast Cancer Progressed After Lapatinib and Trastuzumab Treatment

Phase 2
20 Years
Open (Enrolling)
Metastatic Breast Cancer

Thank you

Trial Information

Randomized Phase II Study of Lapatinib Plus Vinorelbine Versus Vinorelbine in Patients With HER2 Positive Metastatic Breast Cancer Progressed After Lapatinib and Trastuzumab Treatment

This study is a multicenter, randomized, open label, phase II study. Patients will be
randomized to either lapatinib plus vinorelbine (LV) arm or vinorelbine alone (V) arm, if
they are satisfied by inclusion and exclusion criteria. The stratification factors are
followings: 1) visceral metastasis vs. others, 2) previous response to lapatinib treatment,
complete response(CR)+partial response(PR) vs. stable disease(SD)≥ 12wks.

Patients in LV arm will receive daily lapatinib 1,000mg with vinorelbine 20mg/m2 day1 and
day 8. Patients in V arm will receive vinorelbine 30mg/m2 day 1 and day 8. Treatment repeats
every 21 days unless there is any evidence of disease progression or unacceptable toxicity
or noncompliance by patient with protocol requirements. Response will be documented by
physical examination, chest or abdomen CT prior to treatment as a baseline, and every 2
cycles (window period ± 1 week) after a start of treatment and at 18 weeks.

Inclusion Criteria:

- Confirmed stage IV or recurrent breast cancer

- positive for HER2 in tumor cells by immunohistochemistry (3+) or FISH

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Age ≥ 20 years

- Measurable or evaluable disease according to the Response Evaluation Criteria in
Solid Tumors version 1.1

- Patients who were treated with anthracycline based regimens in the adjuvant or
metastatic setting.

- Patients who experienced disease progression after the treatment with lapatinib
containing regimens whose response were more than stable disease (including CR, PR,
SD≥ 12 weeks) during treatment. There is no limitation on the time interval between
the stop of lapatinib treatment and the study enrollment.

- Patients must have received 2 lines of prior anti-HER2 therapy in metastatic setting
as follows regardless of the order In case with trastuzumab: monotherapy or combined
with taxane or combined with AI In case with lapatinib: monotherapy or combined with
capecitabine or combined with aromatase inhibitors Patients who experienced a disease
recurrence during the adjuvant trastuzumab treatment or within 6 months after the
completion of adjuvant trastuzumab treatment are allowed not to receive trastuzumab
treatment in the metastatic setting.

- Central nervous system metastasis is permitted if asymptomatic or controlled with
minimal steroid requirement and is documented to be non-progressing at study entry.

- Negative urine pregnancy test within 7 days prior to registration in premenopausal

- Baseline LVEF ≥50% measured by echocardiogram or multiple gated acquisition scan
(MUGA) scan

- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3,
platelet≥100,000/mm3, hemoglobin≥10g/mm3

- Adequate hepatic function: total bilirubin ≤1.5mg/dL, AST/ALT≤2 x upper normal limit
(UNL), alkaline phosphatase ≤2.5 x UNL, in case with bone metastases alkaline
phosphatase ≤5 x UNL

- Adequate renal function: Serum creatinine ≤1.5mg/dL

- Ability to understand and comply with protocol during study period

- Patients should sign a written informed consent before study entry

Exclusion Criteria:

- Pregnant or lactating women or women of childbearing potential, including women whose
last menstrual period was ,12 months ago (unless surgically sterile) who are unable
or unwilling to use adequate contraceptive measures during the study treatment

- Patients who received vinorelbine treatment in metastatic setting.

- Patients who received more than 2 lines of prior anti-HER2 therapy in metastatic

- Patients who have history of cancer other than in situ uterine cervix cancer or
nonmelanotic skin cancer

- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative

- 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)

- Concurrent disease or serious medical disorder,

- Serious cardiac illness :

History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%)
High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade atrioventricular
(AV)-block,supraventricular arrhythmias, prolonged corrected QT (QTc) which are not
adequately rate-controlled) Angina pectoris requiring antianginal medication Clinically
significant valvular heart disease Evidence of transmural infarction on ECG Poorly
controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg)

- known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to any of the study agents or their excipients.

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 rate at 18 weeks

Outcome Description:

The PFS rate at 18 weeks will be calculated as the ratio of patients on the study to Intent to treat (ITT) population at the time point of 18 weeks from the initiation of study treatment. The ITT population will consist of all patients who are randomized.

Outcome Time Frame:

The time point of 18 weeks from the initiation of study treatment.

Safety Issue:


Principal Investigator

Jungsil Ro

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Center, Korea


South Korea: Institutional Review Board

Study ID:




Start Date:

August 2012

Completion Date:

December 2016

Related Keywords:

  • Metastatic Breast Cancer
  • Lapatinib
  • Vinorelbine
  • Breast Neoplasms