Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: paclitaxel; Biological: trastuzumab; Other: laboratory biomarker analysis; Drug: lapatinib ditosylate; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT00482391

07-013

MSKCC-07013

Details and patient eligibility

About

The purpose of this study is to study a new treatment for HER-2/neu (+) breast cancer.

Enrollment: 95 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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 treatment

• 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 CONCURRENT THERAPY:

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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95 participants in 1 patient group

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

Experimental group

Description:

The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate.

Treatment:

Drug: lapatinib ditosylate

Other: laboratory biomarker analysis

Drug: doxorubicin hydrochloride

Drug: cyclophosphamide

Drug: paclitaxel

Biological: trastuzumab