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Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC -> Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab

Phase 2
18 Years
70 Years
Not Enrolling
Breast Cancer, Metastatic Breast Cancer

Thank you

Trial Information

Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC -> Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab

This trial combines dose dense chemotherapy with Doxorubicin and Cyclophosphamide (AC)
followed by standard every 3 week docetaxel and GW572016 for neoadjuvant treatment of
her2neu positive stage II/III breast cancer. GW572016 or Lapatinib, the investigational
agent, acts as a duel inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2
(Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed
or altered in human cancers including breast cancer. This study plans to determine the
antitumor activity of this regimen and its effectiveness of preventing tumor growth and

The primary objective of the study is to improve pathological complete response rates with
the addition of dual EGFR blockade. Neoadjuvant chemotherapy which achieves pathologic
complete responses (pCR) has been shown to predict improved long-term survival and serves as
a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical
data with smaller patient numbers and at a lower overall cost. Additionally, we hope to
correlate clinical and radiologic outcomes with gene expression data.

Inclusion Criteria:

- Women with histologically confirmed Her2neu positive breast cancer.
Patients are considered Her2Neu positive by either Immunohistochemistry (IHC) 3+ or
Fluorescence In Situ Hybridization (FISH)+

- Stage II/III breast cancer including any large primary tumor (> 2 cm), tumors of any
size associated with skin or chest wall involvement, tumors of any size with axillary
lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or
supraclavicular lymph nodes).

- At least one bidimensional, measurable indicator lesion. All sites of disease should
be noted and followed. Baseline measurements and evaluations of tumor must be done
within 3 weeks prior to initiation of treatment.

- Patients must be between 18 and 70 years of age

- ECOG performance status 2/ Karnofsky > 60% at screening and on the first day of

- Informed consent must be obtained prior to registration.

- Cardiac ejection fraction within the institutional range of normal as measured by
MUGA scan. Note that baseline and on treatment scans should be performed using the
same modality and preferably at the same institutions

- Patients must have normal organ and marrow function as defined below:

- Hematologic (minimal values)

1. Absolute neutrophil count > 1,500/mm3

2. Hemoglobin > 8.0 g/dl

3. Platelet count > 100,000/mm^3

- Creatinine within normal institutional limits

- Hepatic

1. Total Bilirubin equal to or less than ULN

2. AST and ALT and Alkaline Phosphatase must be within the range allowing for

3. In determining eligibility the more abnormal of the two values (AST or ALT)
should be used.

- Eligibility of patients receiving medications or substances known to affect, or with
the potential to affect the activity or pharmacokinetics of GW572016 will be
determined following review of their use by the Principal Investigator

- Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.

- All herbal (alternative) medicines are prohibited. In addition please see
section 6.6 of the protocol regarding medications that are prohibited during the
administration of GW572016 and for the duration of GW572016.

- The effects of GW572016 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control or
abstinence) prior to study entry and for the duration of study participation. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately. Must have negative pregnancy
test if of child bearing years.

- Peripheral neuropathy: must be < grade 1

- Able to swallow and retain oral medication

Exclusion Criteria:- Evidence of disease outside the breast or chest wall, except for
ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.

- Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.

- More than 3 months between histologic diagnosis and registration on this study.

- History of other malignancy within the last five years, except curatively treated
basal cell carcinoma of the skin or carcinoma in situ of the cervix.

- Psychological, familial, sociological or geographical conditions which do not permit
weekly medical follow-up and compliance with the study protocol. Patients who are
medically unstable, including but not limited to active infection, acute hepatitis,
deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding,
uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena
cava syndrome, and patients whose circumstances do not permit completion of the study
or the required follow-up.

- Patients who have congestive heart failure, abnormal LVEF, angina pectoris,
uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had
a myocardial infarction within the past year.

- Pregnant or lactating females, or females of childbearing potential not employing
adequate contraception.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GW572016.

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with GW572016. Appropriate
studies will be undertaken in patients receiving combination anti-retroviral therapy
when indicated.

- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative

- Patients with a history of severe hypersensitivity reaction to Taxotere® or other
drugs formulated with polysorbate 80.

Type of Study:


Study Design:

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

Outcome Measure:

Pathologic complete response

Outcome Time Frame:

1.5 years

Safety Issue:


Principal Investigator

George Albert Fisher M.D. Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Institutional Review Board

Study ID:




Start Date:

October 2006

Completion Date:

March 2011

Related Keywords:

  • Breast Cancer
  • Metastatic Breast Cancer
  • Breast Neoplasms



Stanford University School of Medicine Stanford, California  94305-5317
Santa Clara Valley Medical Center San Jose, California  95128