ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: January 4, 2006
Last updated: October 17, 2013
Last verified: October 2013

Patients will be randomised to a 1:1 ratio to receive either paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV, and oral lapatinib 1000 mg QD or paclitaxel 80 mg/m2 IV weekly for three weeks of a four week cycle, trastuzumab 4 mg/kg loading dose and 2 mg/kg weekly IV plus placebo. The primary objective of this study is to evaluate and compare time to progression (TTP). Secondary objectives will be to evaluate and compare the two treatment arms with respect to: overall response rates, clinical benefit, time to response, duration of response, progression-free survival, and overall survival. The study will first enroll an open label safety cohort of 20 patients to assess the tolerability of the triplet combination.

Condition Intervention Phase
Neoplasms, Breast
Drug: lapatinib
Drug: paclitaxel
Drug: trastuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo-Controlled, Multicenter, Phase III Study Comparing the Activity of Paclitaxel Plus Trastuzumab Plus Lapatinib to Paclitaxel Plus Trastuzumab Plus Placebo in Women With ErbB2 Overexpressing Metastatic Breast Cancer

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Patients have completed at least 16 weeks of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • clinical benefit [ Time Frame: Patients have completed at least 16 weeks of treatment ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: December 2005
Estimated Study Completion Date: December 2015
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Open label safety phase. All patients received paclitaxel + trastuzumab + lapatinib.
Drug: lapatinib
(GW572016) 1000 mg QD
Drug: paclitaxel
80 mg/m2 IV weekly for three weeks
Drug: trastuzumab
4 mg/kg loading dose and 2 mg/kg weekly IV


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Histologically confirmed invasive breast cancer with stage IV disease If trastuzumab was administered in the adjuvant setting, >12 months must have elapsed since discontinuation of trastuzumab therapy
  • If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred 12 months after completion of this treatment
  • Had tumors that overexpress ErbB2 (Immunohistochemistry 3+ or Fluorescent in-situ hybridisation gene amplification)
  • Patients must have tumor tissue available for central testing Measurable lesion(s)
  • Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception
  • Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication
  • Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
  • For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy;
  • Able to swallow and retain oral medication
  • Cardiac ejection fraction within institutional range of normal
  • Patient must have adequate organ function

Exclusion criteria:

  • Pregnant or lactating females;
  • Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization; Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
  • Patients with ulcerative colitis are also excluded;
  • History of other malignancy; however, patients who have been disease-free for five years, or patients 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 patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety;
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
  • Peripheral neuropathy of Grade 2 or greater;
  • Active or uncontrolled infection;
  • Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
  • Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure;
  • Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
  • Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy); Concurrent treatment with an investigational agent or participation in another clinical trial;
  • Concurrent treatment with any medication on the prohibited medications list.
  • Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment.
  • Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting;
  • A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients;
  • A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients;
  • A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients;
  • Non compliance with any of the screening procedures
  Contacts and Locations
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Please refer to this study by its identifier: NCT00272987

  Show 28 Study Locations
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Esteva FJ, Franco SX, Hagan MK, Somer R, Dombroski C, Florance A, Turner S, Stein S, Perez A. An Evaluation of the Safety and Efficacy of Lapatinib Plus Trastuzumab Plus Paclitaxel in First-Line HER2+ Metastatic Breast Cancer. 32nd Annual San Antonio Breast Cancer Symposium. 2009.

Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: GlaxoSmithKline Identifier: NCT00272987     History of Changes
Other Study ID Numbers: EGF104383
Study First Received: January 4, 2006
Last Updated: October 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
metastatic breast cancer
Stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors processed this record on July 28, 2014