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

NCT00482391 | Completed Phase 2 Results

• 2 other identifiers: 07-013MSKCC-07013
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Completed All Planned Therapy

  The number of patients who completed all planned therapy (dose-dense adjuvant/ neoadjuvant chemotherapy regimen) in HER-2/neu-overexpressed/ amplified breast cancer patients.

  2 years

Secondary Outcomes (1)

• Number of Patients Who Were Evaluated for Toxicity

  2 years

Study Arms (1)

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

EXPERIMENTAL

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.

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

Interventions

trastuzumab BIOLOGICAL

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

cyclophosphamide DRUG

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

doxorubicin hydrochloride DRUG

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

lapatinib ditosylate DRUG

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

paclitaxel DRUG

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

laboratory biomarker analysis OTHER

AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Dana-Farber Cancer Institute: collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

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

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (1)

• 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.

  PMID: 20479410 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; Cyclophosphamide; Doxorubicin; Lapatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Chau Dang
• Organization: Memorial Sloan Kettering Cancer Center

dangc@mskcc.org

914-367-7181

Study Officials

• Chau T. Dang, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Clifford A. Hudis, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2007
• First Posted: June 5, 2007
• Study Start: March 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: May 12, 2017
• Results First Posted: March 13, 2017

Record last verified: 2017-04

Locations

US (2)