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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00482391
• Other study ID #: 07-013
• Secondary ID: MSKCC-07013
• Status: Completed
• Phase: Phase 2
• First received: June 4, 2007
• Last updated: March 6, 2013
• Start date: March 2007
• Est. completion date: July 2011

Study information

• Verified date: March 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with trastuzumab and lapatinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin together with cyclophosphamide followed by paclitaxel, trastuzumab, and lapatinib works in treating patients with HER2/neu-overexpressed breast cancer.

Description:

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• lapatinib ditosylate

• paclitaxel

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Dana-Farber Cancer Institute, GlaxoSmithKline, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & 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/am — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility		2 years	No
Secondary	Toxicity		2 years	Yes
Secondary	Time to recurrence		2 years	No
Secondary	Overall survival		2 years	No