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Phase II Clinical Study of Lapatinib (GW572016) in Patients With ErbB2 Over - Expressing Advanced or Metastatic Breast Cancer

Phase 2
20 Years
74 Years
Not Enrolling
Neoplasms, Breast

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Trial Information

Phase II Clinical Study of Lapatinib (GW572016) in Patients With ErbB2 Over - Expressing Advanced or Metastatic Breast Cancer

Inclusion Criteria:

A subject will be considered eligible for inclusion in this study only if all of the
following criteria apply:

- Life expectancy of ≥16 weeks from the start of lapatinib therapy;

- Signed informed consent obtained from the patient;

- Subjects must have histologically confirmed breast cancer with advanced (Stage IIIb,
IIIc with T4 lesion) or metastatic disease (including recurrent patients);

- Subjects must meet the following criteria regarding prior therapy:

- Anthracyclines, taxanes:

- If anthracycline- and taxane-containing regimens are administered sequentially;

- Subjects should have been provided with at least 2 cycles each and at least 4 cycles
in total.

- If anthracycline- and taxane-containing regimen are administered concurrently;

- Subjects should have been provided with at least 4 cycles in total. or

- Subjects should have been provided with at least 2 cycles in total and provided
progressive disease occurred.

- If anthracycline- and taxane-containing regimen are administered separately;

- Subjects should have been provided with at least 4 cycles each. or

- Subjects should have been provided with at least 2 cycles each and provided
progressive disease occurred each regimen.

- Trastuzumab:

- Prior treatment must contain trastuzumab alone or in combination with other
chemotherapy for at least 6 weeks of standard doses.

- Subjects must meet the following criteria regarding ErbB2 expression (defined by the
following status before undergoing trastuzumab therapy.)

Patients with ErbB2 overexpression:

- 3+ by IHC, or FISH+

- 2+ by IHC and FISH+ are also eligible. However, patients with "2+ by IHC" who have
previously been treated with trastuzumab should undergo FISH before study entry, if
they have not had this test performed before, and are considered eligible only if
their tumours are categorised as FISH+.

- Documentation of tumor progression or relapse after the most recent treatment is

- Archived tumor tissue must be available to compare tumor response with intra-tumoral
expression levels of biomarkers (ErbB1 and ErbB2).

- Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid
Tumors); (See "6.3. Efficacy")

- A female, ≥20 and ≤74 years (at the time of giving consent), is eligible to enter and
participate in this study if she is of:

- Non-childbearing potential (i.e., women with functioning ovaries who have a current
documented tubal ligation or hysterectomy, or women who are post-menopausal, i.e., at
least 1 year has past since the last menstrual period); or is

- The subject has a negative serum pregnancy test at screening, and agrees to one of
the following from 2 weeks prior to administration of the first dose of lapatinib
until 28 days after the final dose of lapatinib*.

- Complete abstinence from intercourse:

- Consistent and correct use of one of the following acceptable methods of birth

- Injectable progestogen;

- Any intrauterine device (IUD);

- Oral contraceptives (either combined or Progestogen only);

- Barrier methods including diaphragm or condom with a spermicide.

- At least 3 weeks since the last dose of prior last chemotherapy, immunotherapy,
biologic therapy, hormonal therapy, or radiotherapy (except for local radiation
therapy to pain relief) for cancer or since the date of completion of surgery (except
for minor surgical procedures) before beginning treatment with lapatinib, except for
trastuzumab which must be discontinued at least 2 weeks prior to beginning of study
drug. Subjects must have recovered or stabilized sufficiently from side effects
associated with prior therapy;

- Prior to enrollment, radiation therapy is allowed to a limited field (e.g. painful
bone mets, painful lumps), if it is not the sole site of measurable and/or assessable
disease. Patients must have completed treatment and adequately recovered, in
particular from bone marrow suppression.

- Subjects who are not on bisphosphonate therapy. Bisphosphonates initiated prior to
study medication are allowed; however, initiation of bisphosphonate following the
first dose of study medication is not allowed. Prophylactic use of bisphosphonates
is only permitted for treatment of osteoporosis.

- Subjects with stable CNS metastasis (asymptomatic and off systemic steroids and
anticonvulsants for at least 3 months) are also eligible;

- ECOG Performance Status of 0 to 2;

- Able to swallow and retain oral medication;

- Left ventricular ejection fraction (LVEF), measured by echocardiogram (ECHO), above
the institutional's lower limit of normal (LVEF of ≥50% in such case as normal range
of LVEF is not provided by institution).

- Subjects must have adequate organ function as defined below:

- Myelofunction:

Neutrophil count ≥1500 /mm3 Hemoglobin ≥9 g/dL (at least 2 weeks after blood transfusion
if needed) Platelet count ≥100,000 /mm3

- Hepatic function:

Albumin ≤2.5 g/dL Total bilirubin ≤1.5xULN AST, ALT: ≤3xULN (without liver metastases),
≤5xULN (if documented liver metastases)

- Renal function:

Serum creatinine ≤1.5 mg/dL, or creatinine clearance ≤40 mL/min (calculated by the
Cockcroft and Gault Method)

- Subjects who can visit the hospital once weekly (±3 days) at least in the first month
after the start of lapatinib therapy and then every 4 weeks (±1 week) until the last

Exclusion Criteria:

A subject will not be eligible for inclusion in this study if any of the following
criteria apply:

- Pregnant or lactating females;

- Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel. Subjects with ulcerative colitis are also

- History of other malignancy. Subjects who have been disease free for 5 years, or
subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible;

- 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 * [* ≥Grade 3 (according to NCI-CTCAE Version 3.0), as a general

- Active or uncontrolled infection;

- Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart

- Known history of or clinical evidence of leptomeningeal carcinomatosis;

- Participated in a clinical study within the past 28 days of the first dose of

- Prior therapy with an ErbB1inhibitor (e.g., gefinitib) and/or ErbB2 inhibitor other
than trastuzumab;

- Has taken/received prohibited inhibitors (including foods) of CYP3A4 within 7 days
prior to the first dose of study medication or has taken/received prohibited inducers
inducers (including foods) of CYP3A4 within 14 days prior to the first dose of study
medication(Refer to Appendix 7).

- The subject has a known immediate or delayed hypersensitivity reaction or
idiosyncrasy to drugs chemically related to lapatinib or excipients

- Patients ineligible for participation in the study in the judgment of the
investigator/sub investigator.

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:

Overall Tumor Response

Outcome Description:

Tumor response was measured as the number of participants achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) among all participants who received study treatment. Tumor response was evaluated as the best response in accordance with response evaluation criteria in solid tumors (RECIST). Progressive disease: a 20% increase in the sum of the longest diameter of target lesions. Stable disease: small changes that do not meet the above-mentioned criteria.

Outcome Time Frame:

Baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Japan: Ministry of Health, Labor and Welfare

Study ID:




Start Date:

November 2005

Completion Date:

April 2009

Related Keywords:

  • Neoplasms, Breast
  • Stage IV breast cancer
  • Herceptin
  • metastatic breast cancer
  • ErbB1
  • ErbB2
  • trastuzumab
  • lapatinib
  • Breast Neoplasms
  • Neoplasms