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

NCT ID: NCT00482391

Last Updated: 2017-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2011-07-31

Brief Summary

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

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

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.

Group Type: EXPERIMENTAL

trastuzumab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

lapatinib ditosylate

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Interventions

trastuzumab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

lapatinib ditosylate

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chau T. Dang, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Clifford A. Hudis, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Dang C, Lin N, Moy B, Come S, Sugarman S, Morris P, Abbruzzi A, Chen C, Steingart R, Patil S, Norton L, Winer E, Hudis C. Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea. J Clin Oncol. 2010 Jun 20;28(18):2982-8. doi: 10.1200/JCO.2009.26.5900. Epub 2010 May 17.

Reference Type: RESULT

PMID: 20479410 (View on PubMed)

Other Identifiers

MSKCC-07013

Identifier Type: -

Identifier Source: secondary_id

07-013

Identifier Type: -

Identifier Source: org_study_id