Know Cancer

forgot password

A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib (GW572016) in Women With Early-Stage ErbB2 Overexpressing Breast Cancer

Phase 3
18 Years
Open (Enrolling)
Neoplasms, Breast

Thank you

Trial Information

A Randomized, Double-blind, Multicenter, Placebo-controlled Study of Adjuvant Lapatinib (GW572016) in Women With Early-Stage ErbB2 Overexpressing Breast Cancer

Inclusion Criteria:

- Have histologically or cytologically confirmed ErbB2-overexpressing invasive
carcinoma (TX or T1-4) of the breast at the time of the initial diagnosis and have
undergone adequate excision of tumor;

- Had tumors that overexpress ErbB2 defined as 3+ by IHC or c-erbB2 gene amplification
by FISH (ErbB2 expression/amplification must be documented prior to study entry;
however, a tumor tissue sample must be sent to a central laboratory for subsequent
re-analysis of ErbB2 status);

- Have Stage I through Stage IIIc disease according to the American Joint Committee on
Cancer (6th edition) staging criteria for breast cancer and meet one of the following

node-positive disease defined as: one positive lymph node by sentinel node biopsy OR at
least 1 positive lymph node found among at least 6 axillary nodes examined on axillary
node dissection OR status post axillary radiotherapy for sterilization if clinically
evaluated as cN1 or cN2 (if sentinel node biopsy is positive, subject may either undergo
an axillary node dissection or radiotherapy to the axilla).

node-positive disease evaluated as: ipsilateral axillary lymph nodes cN0-2 by clinical
evaluation and axillary lymph nodes pNX, pN0(i+), or pN1-3 by pathological evaluation
[patients with pN3 (Stage IIIc disease) must be disease free following completion of
neoadjuvant or adjuvant chemotherapy for at least 12 months and must not have been lost to
follow up].

OR node-negative disease defined as: negative sentinel node biopsy OR no positive lymph
nodes found among at least 6 axillary nodes examined on axillary node dissection OR status
post axillary radiotherapy for sterilization if clinically evaluated as cN0.

node-negative disease categorized as: high-risk disease (tumor >2.0 cm if ER and/or
progesterone receptor (PgR) positive disease is present or tumor >1.0 cm if ER and PgR
negative disease) OR intermediate-risk disease (tumor 1.0-2.0 cm and ER and/or PgR
positive disease).

- Women with synchronous bilateral invasive breast cancer or synchronous DCIS of either
the contralateral or ipsilateral breast at the time of the initial diagnosis are also

- Have undergone either mastectomy OR lumpectomy;

- Have received and completed treatment with a neoadjuvant or adjuvant chemotherapy
regimen containing either an anthracycline or a taxane; or any cyclophosphamide,
methotrexate and 5-fluorouracil (CMF) regimen;

- May continue to receive endocrine therapy while taking study medication, if endocrine
therapy was initiated as either adjuvant therapy for treatment of the initial
diagnosis of invasive breast cancer or for ovarian function suppression; however,
endocrine therapy may not be initiated while taking study medication. Endocrine
therapy agents may be switched while participating in this study (e.g., stop
tamoxifen and start letrozole);

- May have received prior radiotherapy as treatment for primary tumor; however, is not
required for study entry;

- May continue to receive radiotherapy while taking study medication, if radiotherapy
was initiated as adjuvant therapy for treatment of the initial diagnosis of invasive
breast cancer;

- May continue to receive bisphosphonates only for treatment of documented
osteoporosis, but not as treatment or prophylaxis of bone metastases;

- All women eligible for adjuvant treatment with trastuzumab, including those diagnosed
and treated within the last six months, must be considered for such treatment prior
to being offered participation in this study. Participation in this study will be
allowed only if the physician and patient have considered and discussed at length the
advantages of trastuzumab, but have mutually decided against initiating trastuzumab

- Have clinical and radiologic assessments that are negative for local or regional
recurrence of disease or metastatic disease at the time of study entry;

- if signs or symptoms suggestive of either recurrence of disease or metastatic disease
are present, the appropriate radiological imaging must be performed

- if the following laboratory results are present, the appropriate radiological imaging
must be performed:

- for AST/ALT ≥2×ULN or ALP ≥2×ULN (not in the bone fraction), an abdominal CT or MRI
must be done

- for ALP≥2×ULN in the bone fraction, a bone scan must be done; a confirmatory x-ray,
CT scan or MRI scan or biopsy is required if the results of the bone scan are

- Have a unilateral/bilateral mammogram within 12 months prior to study entry;

- Have an analysis of both ER and PgR on the primary tumor prior to study entry;

- Have a cardiac ejection fraction within institutional range of normal as measured by
either echocardiogram or multigated acquisition scans;

- Have an Eastern Cooperative Oncology Group Performance Status of 0 to 1;

- Women with a history of non-breast malignancies are eligible if they have been
disease-free for at least 5 years and are deemed by the investigator to be at low
risk for recurrence. Women with the following cancers are eligible if diagnosed and
treated within the past 5 years: cervical carcinoma in situ, melanoma in situ, and
basal cell or squamous cell carcinoma of the skin;

- Are able to swallow and retain oral medication;

- Have a paraffin-embedded tissue block from an archived tumor tissue from the primary
tumor or twenty (20) slides of paraffin-embedded tissue available for biomarker

- Have adequate organ function defined as: absolute neutrophil count ≥1.5× 10^9/L;
hemoglobin ≥9 g/dL; platelets ≥75 × 10^9/L; albumin ≥2.5 g/dL; serum bilirubin ≤1.25
×ULN; aspartate aminotransferase and alanine aminotransferase ≤3 × ULN and serum
creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥40 mL/min

- Have signed the informed consent form (ICF);

- Women of child-bearing potential must have a negative serum pregnancy test at
screening and agree to complete abstinence from intercourse or consistent and correct
use of an acceptable methods of birth control from 2 weeks prior to administration of
the first dose of study medication until 28 days after the final dose of study

Exclusion Criteria:

- Have clinical and radiologic evidence of local or regional recurrence of disease or
metastatic disease at the time of study entry;

- Had metachronous invasive breast cancer (breast cancers diagnosed at different

- Have a prior history of other breast cancer malignancies, including DCIS;

- Are unable to provide archived tumor tissue samples for assay;

- Had prior therapy with an ErbB1 and/or ErbB2 inhibitor; women who experienced a
hypersensitivity or allergic reaction to trastuzumab during the first infusion and
were unable to complete this infusion are eligible;

- Receive concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic
therapy) while taking study medication;

- Have unresolved or unstable, serious toxicity from prior administration of another
investigational drug and/or of prior cancer treatment;

- Have malabsorption syndrome, disease significantly affecting gastrointestinal
function, or resection of the stomach or small bowel. Women with ulcerative colitis
are also excluded;

- Have a concurrent disease or condition that would make the woman inappropriate for
study participation, or any serious medical disorder that would interfere with the
woman's safety;

- Have an active or uncontrolled infection;

- Have dementia, altered mental status, or any psychiatric condition that would
prohibit the understanding or rendering of informed consent;

- Have a known history of uncontrolled or symptomatic angina, arrhythmias, or CHF;

- Are pregnant or breastfeeding;

- Receive concurrent treatment with an investigational agent; women, who are in
follow-up in another clinical trial where the primary endpoint has been met and the
interval between assessments is ≥12 months and radiological imaging is not required
at these assessments, are eligible;

- Receive concurrent treatment with a selected list of strong inducers and inhibitors
of CYP3A4;

- Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
preceding the first dose of study medication;

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to lapatinib or excipients;

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Disease-free survival defined as the interval between the date of randomization and the date of objective disease recurrence, a second primary cancer, or death from any cause

Outcome Time Frame:

During the 12 month treatment period assessments are done every 3 months. During the 10 year follow-up, assessments are every 3, 6 or 12 months (dependent upon time from initial diagnosis)

Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

July 2006

Completion Date:

April 2019

Related Keywords:

  • Neoplasms, Breast
  • Breast Cancer
  • ErbB2-overexpressing
  • early-stage breast cancer
  • adjuvant
  • Breast Neoplasms
  • Neoplasms



GSK Investigational Site Phoenix, Arizona  85013 - 4496
GSK Investigational Site Little Rock, Arkansas  72205
GSK Investigational Site Bakersfield, California  93309
GSK Investigational Site Gainesville, Florida  32610
GSK Investigational Site Indianapolis, Indiana  46260
GSK Investigational Site Lexington, Kentucky  40536-0098
GSK Investigational Site New Orleans, Louisiana  70112
GSK Investigational Site Scarborough, Maine  04074
GSK Investigational Site Springfield, Massachusetts  01107
GSK Investigational Site Duluth, Minnesota  55805
GSK Investigational Site St. Louis, Missouri  63141
GSK Investigational Site Raleigh, North Carolina  27609
GSK Investigational Site Akron, Ohio  44304
GSK Investigational Site Fort Worth, Texas  76104
GSK Investigational Site Park Ridge, Illinois  60068
GSK Investigational Site Bettendorf, Iowa  52722
GSK Investigational Site Baltimore, Maryland  21201
GSK Investigational Site Hooksett, New Hampshire  03106
GSK Investigational Site Pittsburgh, Pennsylvania  15213
GSK Investigational Site Columbia, South Carolina  29210
GSK Investigational Site Germantown, Tennessee  38138
GSK Investigational Site Salem, Virginia  24153
GSK Investigational Site New York, New York  10021
GSK Investigational Site Aurora, Colorado  80012
GSK Investigational Site Hartford, Connecticut  06106
GSK Investigational Site Washington, District of Columbia  20307-5001
GSK Investigational Site Kansas City, Kansas  66160
GSK Investigational Site Edison, New Jersey  08837
GSK Investigational Site Salt Lake City, Utah  84107
GSK Investigational Site Seattle, Washington  98133