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Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility



- Determine the feasibility of dose-dense doxorubicin hydrochloride and cyclophosphamide
followed by paclitaxel, trastuzumab (Herceptin®), and lapatinib ditosylate in patients
with HER2/neu-overexpressed/amplified breast cancer.


- Assess the toxicity of this regimen in these patients.

- Determine the time to recurrence in patients treated with this regimen.

- Determine the overall survival of patients treated with this regimen.

- Explore the use of serial troponin I (cTnI) and C-reactive protein (CRP) as a predictor
of cardiac toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients may receive therapy as neoadjuvant or
adjuvant administration. Chemotherapy must be completed before breast surgery in case of
neoadjuvant therapy. Adjuvant therapy must begin within 84 days after breast surgery.

- Chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on
day 1. Treatment repeats every 2 weeks for 4 courses. Patients then receive paclitaxel
IV once weekly for 12 weeks.

- Trastuzumab (Herceptin®) and lapatinib ditosylate: Beginning concurrently with
paclitaxel, patients receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks
and then once every 3 weeks, beginning at least 1 week after completion of paclitaxel,
for a total of 52 weeks. Patients also receive oral lapatinib ditosylate once daily,
beginning concurrently with paclitaxel, for a total of 52 weeks.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, every 2 weeks during chemotherapy, and at 6, 9, and
18 months. Samples are examined for serial troponin and C-reactive protein.

After completion of study treatment, patients are followed every 3-6 months for 3 years,
every 6 months for 2 years, and then annually thereafter.

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the breast

- Bilateral synchronous breast tumors allowed

- Any nodal status or tumor size allowed

- No stage IV disease

- HER2/neu-positive disease

- 3+ by IHC OR FISH-amplified

- Hormone receptor status not specified


- Male or female

- Menopausal status not specified

- ECOG performance status 0-1

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.1 mg/dL

- SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and after completion
of study therapy

- LVEF ≥ 50% by MUGA scan

- No peripheral neuropathy > grade 1

- No active second malignancy within the past 5 years except for adequately treated
nonmelanoma skin cancer or in situ carcinoma of the cervix

- No known allergy or hypersensitivity to doxorubicin hydrochloride, cyclophosphamide,
paclitaxel, or other drugs formulated in Cremophor EL

- No psychiatric illness or concurrent medical conditions that would preclude study

- No other conditions, including any of the following:

- Unstable angina

- Congestive heart failure

- Myocardial infarction within the past 12 months

- High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade AV
block, or supraventricular arrhythmias that are not adequately controlled)

- No QT prolongation (> 500 ms)

- No active unresolved infections

- No sensitivity to E. coli derived proteins


- Prior hormonal therapy for chemoprevention allowed

- No prior trastuzumab (Herceptin®)

- No prior anthracyclines

- No concurrent hormonal therapy, including hormonal contraception (e.g., birth control
pills or ovarian hormonal or replacement therapy)

- No other concurrent chemotherapy, radiotherapy, immunotherapy, or biotherapy for
breast cancer

- No concurrent drugs that may prolong the QT

Type of Study:


Study Design:

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

Outcome Measure:


Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Chau T. Dang, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

March 2007

Completion Date:

July 2011

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • male breast cancer
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115