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A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer

Phase 2
18 Years
Not Enrolling
Neoplasms, Breast, Breast Cancer

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Trial Information

A Phase II Study to Evaluate the Efficacy, Safety and Pharmacodynamics of Lapatinib in Patients With Relapsed or Refractory Inflammatory Breast Cancer

This Phase II open label, multicenter study is designed to evaluate the efficacy, safety,
and pharmacodynamic effects of oral lapatinib administered as a single agent therapy to
patients with relapsed or refractory inflammatory breast cancer. Eligible patients must
have a diagnosis of inflammatory breast cancer based on clinicopathologic criteria, tumor
that is readily accessible for biopsy, and must have previously received treatment with an
anthracycline and taxane-containing regimen (30 patients) plus trastuzumab (90 patients).
Patients enrolled must have tumors that overexpress ErbB2, with or without co-expression of
ErbB1. The primary objective for this study is to evaluate the objective response rate
(defined as complete response plus partial response). Secondary objectives are to evaluate
clinical benefit including quality of life parameters, progression-free survival, overall
survival, time-to-response, response duration, safety and tolerability, pharmacodynamic
effects on intracellular mediators that regulate tumor cell growth and survival, as well as
effects on proteomic profile, and circulating levels of extracellular domains of ErbB1 and
ErbB2 in peripheral blood.

Inclusion Criteria

Inclusion criteria:

- Must have a life expectancy of at least 12 weeks.

- Has a left ventricular ejection fraction (LVEF) ≥ 50%, or ≥ lower limit of normal for
the institution, based on ECHO or MUGA.

- Aspartate and alanine transaminase (AST or ALT) ≤ 3 times the upper limit of the
reference range (patients with liver metastases may have AST and ALT ≤ 5 times the
upper limit of the reference range and may be enrolled).

- Total bilirubin ≤ 3.0 mg/dL.

- Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance (CrCl) ≥ 30 mL/min

- Adequate bone marrow function. Hemoglobin ≥ 9 gm/dL. Absolute granulocyte count ≥
1,500/mm³ (1.5 x 10^9/L). Platelets ≥ 75,000/mm³ (100 x 10^9/L).

- Recovered or stabilized sufficiently from side effects associated with previous
chemotherapy, surgery or radiotherapy.

- Provided written informed consent.

- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.

- Able to swallow and retain oral medication.

- Male or female, if female:

A female is eligible to enter and participate in the study if she is of:

1. Non-childbearing potential (i.e., women with functioning ovaries who have a current
documented tubal ligation or hysterectomy, or women who are postmenopausal); or

2. Childbearing potential (i.e., women with functioning ovaries and no documented
impairment of oviductal or uterine function that would cause sterility. This category
includes women with oligomenorrhoea (severe), women who are perimenopausal, and young
women who have begun to menstruate), has a negative serum pregnancy test at
screening, and agrees to one of the following where considered acceptable to the
local IRB/IEC: Double-barrier contraception (condom with spermicidal jelly, foam
suppository, or film; diaphragm with spermicide; or male condom and diaphragm).

Abstinence from sexual intercourse from 2 weeks prior to administration of the
investigational product, throughout the active study treatment period, and through the
post-treatment follow-up visit (to occur 28 days after last dose of investigational

Male partner who is sterile prior to the female subject's entry into the study and is the
sole sexual partner for that female subject.

Implants of levonorgestrel. Injectable progestogen. Any intrauterine device (IUD) with a
documented failure rate of less than 1% per year.

Oral contraceptives (either combined or progestogen only). Barrier methods including
diaphragm or condom with a spermicide.

- At least 18 years of age.

- Has either measurable disease by Response Evaluation Criteria in Solid Tumors
(RESIST) or clinically evaluable skin disease. Measurable lesions may be in the
field of prior adjuvant irradiation; however, there must be at least an 8 week period
between the last radiation treatment and the baseline scan documenting disease status
for the lesion to be measurable.

- Tumor that is accessible for biopsy.

- Tumor that overexpresses ErbB2 defined as 3+ by IHC or FISH +. The ErbB 2
overexpression must be documented prior to dosing.

- Documented disease progression or relapse following treatment, which must have
contained a taxane and anthracycline-containing regimen in the adjuvant or metastatic
setting (30 patients) plus trastuzumab (90 patients)

- Histological diagnosis of breast carcinoma with a clinical diagnosis of IBC based on
the presence of inflammatory changes in the involved breast, including diffuse
erythema and edema (peau d'orange), with or without an underlying palpable mass
involving the majority of the skin of the breast. Pathologic evidence of dermal
lymphatic invasion should be noted but is not required for diagnosis.

Exclusion criteria:

- Is clinically assessed to have inadequate venous access for protocol-related blood

- Has a clinically significant electrocardiogram (ECG) abnormality.

- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.

- Has physiological, familial, sociological, or geographical conditions that do not
permit compliance with the protocol.

- Is currently receiving oral steroid treatment (inhaled steroids are permitted), or
any other medication on the prohibited medications list

- Is currently receiving amiodarone or has received amiodarone in the 6 months prior to

- Has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within
the past 14 days, with the exception of mitomycin C within the past 6 weeks.

- Has received treatment with any investigational drug in the previous 4 weeks.

- Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the investigational product. These include other
anilinoquinazolines, such as gefitinib [Iressa], erlotinib [Tarceva], or other
chemically related compounds.

- Is considered medically unfit for the study by the investigator as a result of the
medical interview, physical exam, or screening investigations.

- Has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal
disease. Patients with brain metastases treated by surgery and/or radiotherapy are
eligible if neurologically stable and do not require steroids or anticonvulsants.

- Has malabsorption syndrome, a disease affecting gastrointestinal function, or
resection of the stomach or small bowel.

- Is a pregnant or lactating female.

Type of Study:


Study Design:

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

Outcome Measure:

Objective Response rate (complete response plus partial response)

Outcome Time Frame:

Week 84

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2005

Completion Date:

December 2008

Related Keywords:

  • Neoplasms, Breast
  • Breast Cancer
  • refractory inflammatory breast cancer
  • relapsed breast cancer
  • ErbB2 overexpressing
  • ErbB1 expressing
  • Breast Neoplasms
  • Neoplasms
  • Inflammatory Breast Neoplasms



GSK Investigational Site Gainesville, Florida  32610
GSK Investigational Site St. Louis, Missouri  63141
GSK Investigational Site Raleigh, North Carolina  27609
GSK Investigational Site Park Ridge, Illinois  60068
GSK Investigational Site Baltimore, Maryland  21201
GSK Investigational Site Seattle, Washington  98133