Know Cancer

forgot password

An Open-label, Single-arm, Phase I/II Study of Lapatinib in Combination With Weekly Paclitaxel as First-line Chemotherapy for ErbB2-overexpressing Metastatic Breast Cancer Patients

Phase 2
18 Years
Open (Enrolling)
Neoplasms, Breast

Thank you

Trial Information

An Open-label, Single-arm, Phase I/II Study of Lapatinib in Combination With Weekly Paclitaxel as First-line Chemotherapy for ErbB2-overexpressing Metastatic Breast Cancer Patients

This is an open-label, single-arm, Phase I/II study to evaluate the efficacy, safety and
tolerability of weekly paclitaxel and lapatinib in subjects with ErbB2-overexpressing
advanced or metastatic breast cancer who have not received prior therapy for metastatic
disease. These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week
cycle) plus lapatinib (1500 mg once daily). Subjects will receive a daily dose of lapatinib
until disease progression or withdrawal from study treatment due to unacceptable toxicity or
withdrawal of consent. Subjects will be treated with paclitaxel for standard of 6 cycles,
and may be continued at the discretion of investigators. If the subject experiences
progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib
therapy, paclitaxel therapy must be terminated any time of study period, even before 6
cycles of paclitaxel are given.

This study consists of the Phase I and Phase II parts:

Phase I part

Tolerability and pharmacokinetics in 6 subjects will be evaluated in Phase I part of study
and the tolerability criteria are set as follow:

Tolerability criteria in first cycle; Concerning the safety tolerability of this trial, if 1
out of 6 first enrolled subjects meets the tolerability criteria, the study will proceed to
phase II part and the regimen will judged as well tolerable. If 2 subjects meet the
tolerability criteria, the sponsor will consult the safety review committee. GSK will
finally judge based on the consultation regarding the tolerability and the medical

Grade 4 hematologic toxicities. Thrombocytopenia less than or equal to 25,000/mm3 Grade 3 or
4 and clinically significant non-haematologic toxicities. Inability to start cycle 2 within
2 weeks of scheduled dosing due to unresolved toxicity.

For all 6 subjects enrolled, safety profiles occurred in cycle 1 are closely monitored
individually. When considering the appropriateness of study continuation, not only the
safety profiles noted in cycle 1 of this study, but also the safety profiles reported from
pilot part of EGF104578 study and other relevant studies will be referred in order to make
medical decisions.

Phase II part After tolerability in 6 subjects enrolled in Phase I part is confirmed,
further 6 subjects to be enrolled for Phase II part (i.e. total of 12 subjects). Subjects
will receive a daily dose of lapatinib until disease progression or withdrawal from study
treatment due to unacceptable toxicity or withdrawal of consent. All 12 subjects will be
followed for survival.

Inclusion Criteria:

- Prior written consent in participating in the study by the subject or his/her proxy

- Japanese female >=18 years of age.

- Invasive breast cancer with stage IV disease.

- Documentation by local laboratory of ErbB2 status by immunohistochemistry (IHC) or
amplification by fluorescence in situ hybridization (FISH).

- If a taxane had been administered in the neoadjuvant or adjuvant setting, progression
must have occurred >12 months after completion of this treatment and the patients
recovered from all associated toxicities.

- Measurable lesion(s) according to RECIST criteria.

- Radiotherapy as palliative treatment for painful metastatic disease is permitted but
must have been stopped within 2 weeks prior to initiation of any investigational

- For those patients whose disease is ER+ and/or PR+ one of the following criteria
should be met:

- Patient with visceral disease that requires chemotherapy (e.g., patients with
liver or lung metastases).

- Rapidly progressing or life threatening disease that are considered to be
inapplicable to hormonal therapy, as determined by the investigator.

- Patients who received hormonal therapy and are no longer benefiting from this
therapy and the hormonal treatment must have been stopped before the first dose
of investigational treatment.

- Subjects recovered from all the associated toxicities by prior endocrine

- Eastern cooperative oncology group (ECOG) Performance status (PS) of 0 or 1.

- Able to swallow and retain oral medication.

- Cardiac ejection fraction within institutional range of normal as measured by
echocardiogram. MUGA scan is accepted in cases where an echocardiogram cannot be
performed or is inconclusive.

- Adequate organ function.

Exclusion Criteria:

- Pregnant or lactating females at anytime during the study.

- Received prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2
therapy for metastatic disease.

- History of other malignancy.

- Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab, in the
adjuvant setting.

- Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy,
immunotherapy, biologic therapy, hormonal therapy) while taking investigational

- Used an investigational drug within 30 days or five half-lives, whichever is longer,
preceding the first dose of investigational treatment.

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

- Uncontrolled infection.

- Patients having at least postive antibody either to HBs or HBc.

- Patients who have had a positive HCV antibody.

- Peripheral neuropathy grade 2 or greater.

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

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

- Known history or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis.

- 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

- Known history or concurrent condition of uncontrolled or symptomatic angina,
arrhythmias, or congestive heart failure.

- Concurrent treatment with prohibited medications.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to paclitaxel or lapatinib or their excipients.

- 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).

Type of Study:


Study Design:

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

Outcome Measure:


Outcome Description:

This regimen is established as the tolerable treatment option for Japanese patients.

Outcome Time Frame:

For first cycle (4 weeks)

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Japan: Ministry of Health, Labor and Welfare

Study ID:




Start Date:

April 2010

Completion Date:

June 2014

Related Keywords:

  • Neoplasms, Breast
  • advanced/metastatic breast cancer
  • lapatinib
  • ErbB2
  • ErbB2-overexpressing
  • pharmacokinetics
  • dual kinase inhibitor
  • HER-2/neu
  • EGFR
  • ErbB1
  • Breast Neoplasms
  • Neoplasms