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

April 6, 2017 updated by: Memorial Sloan Kettering Cancer Center

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

95

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: cyclophosphamide
Other: laboratory biomarker analysis
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Biological: trastuzumab
Drug: lapatinib ditosylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Who Completed All Planned Therapy
Time Frame: 2 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients Who Were Evaluated for Toxicity
Time Frame: 2 years
Please see adverse event section in the results. Toxicities were assessed by the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)
GlaxoSmithKline
Dana-Farber Cancer Institute

Investigators

  • Principal Investigator: Chau T. Dang, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

June 4, 2007

First Submitted That Met QC Criteria

June 4, 2007

First Posted (Estimate)

June 5, 2007

Study Record Updates

Last Update Posted (Actual)

May 12, 2017

Last Update Submitted That Met QC Criteria

April 6, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-013
  • MSKCC-07013

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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