Trastuzumab or Observation After Combination Chemotherapy and Trastuzumab in Treating Patients Undergoing Surgery for Stage II or Stage III Breast Cancer

August 23, 2013 updated by: Instituto Nacional de Cancerologia, Columbia

Adjuvant Trastuzumab vs Observation in Locally Advanced Breast Cancer Treated With Neoadjuvant Trastuzumab

RATIONALE: Drugs used in chemotherapy 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. Giving combination chemotherapy together with trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving trastuzumab after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether trastuzumab is more effective than observation when given after combination chemotherapy and trastuzumab in treating patients with breast cancer.

PURPOSE: This randomized phase II trial is studying trastuzumab to see how well it works compared with observation when given after combination chemotherapy and trastuzumab in treating patients undergoing surgery for stage II or stage III breast cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the percentage of pathological responses in patients with stage II or III breast cancer treated with neoadjuvant therapy comprising fluorouracil, doxorubicin hydrochloride, and cyclophosphamide followed by trastuzumab (Herceptin®) and paclitaxel.
  • To compare the disease-free survival of patients treated with adjuvant therapy comprising trastuzumab versus observation.

Secondary

  • To measure the overall survival at 3 years in these patients.
  • To measure the cardiac safety profile of these regimens in these patients.
  • To measure the percentage of patients that become negative on the fluorescence in situ hybridization (FISH) test at the end of neoadjuvant therapy.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I :

    • Neoadjuvant therapy: Patients receive fluorouracil IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab (Herceptin®) IV over 30-90 minutes and paclitaxel IV over 1 hour once a week for 12 weeks.

After completion of neoadjuvant therapy, patients proceed to surgery.

  • Surgery: Patients undergo definitive surgery. Some patients may also undergo radiotherapy*.

NOTE: *Patients with initial tumor > 5 cm, inflammatory breast cancer, or with a skin condition or final pathological evaluation of metastasis to > 4 nodes or 1-3 nodes with capsular ruptures or extension to fatty tissues receive adjuvant radiotherapy.

  • Adjuvant therapy: Beginning 4 weeks after surgery, patients receive trastuzumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 13 courses.

    • Arm II:
  • Neoadjuvant therapy: Patients receive neoadjuvant therapy as in arm I.
  • Surgery: Patients undergo definitive surgery. Some patients may also undergo radiotherapy if clinically indicated.
  • Observation: Beginning 4 weeks after surgery, patients undergo observation. In both arms, patients with estrogen receptor- and/or progesterone receptor-positive disease also receive anastrozole daily for 5 years. Premenopausal patients with remaining ovarian function (as confirmed by follicle-stimulating hormone [FSH] and estradiol) after completion of anastrozole undergo chemical or surgical ovarian ablation.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year thereafter.

PROJECTED ACCRUAL: A total of 160 patients (80 per treatment arm) will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

160

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

  • Mexico
    • Distrito Federal
      • Mexico City, Distrito Federal, Mexico, 14000
        • Recruiting
        • Instituto Nacional de Cancerologia
        • Contact:
          • Claudia Arce-Salinas, MD
          • Phone Number: 52-55-5628-0400
      • Mexico City, Distrito Federal, Mexico, C.P. 06726
        • Recruiting
        • Hospital General de Mexico
        • Contact:
          • Contact Person
          • Phone Number: 52-55-5999-6133

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 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer by needle biopsy

    • Diagnosed within the past 4 weeks
    • Clinical stage IIB, IIIA, IIIB, or IIIC disease
  • Palpable adenopathies present

  • HER2/neu-positive disease, as evidenced by either of the following:

    • HER2/neu overexpression (3+) by immunohistochemistry (IHC)
    • HER2/neu amplification by fluorescence in situ hybridization (FISH)
  • No metastatic disease by chest radiography, hepatic ultrasound, and bone scan (metastatic bone series if no nuclear medicine is available)

  • Hormone receptor status:

    • Estrogen receptor and/or progesterone receptor status known

PATIENT CHARACTERISTICS:

  • Premenopausal or postmenopausal
  • WHO performance status 0-2
  • Not pregnant or nursing
  • Normal hepatic, renal, and hematological function
  • LVEF ≥ 55% by nuclear medicine study or echocardiogram
  • No prior history of cancer, except carcinoma in situ of the cervix
  • No allergic reaction or hypersensitivity to paclitaxel and/or trastuzumab (Herceptin®)

PRIOR CONCURRENT THERAPY:

  • No prior cancer therapy

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: RANDOMIZED
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease-free survival
Percentage of pathological responses

Secondary Outcome Measures

Outcome Measure
Overall survival at 3 years
Cardiac toxicity
Percentage of patients that become negative on the fluorescence in situ hybridization (FISH) test at the end of neoadjuvant therapy

Collaborators and Investigators

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

Sponsor

Instituto Nacional de Cancerologia, Columbia

Investigators

  • Principal Investigator: Claudia Arce-Salinas, MD, Instituto Nacional de Cancerologia, Columbia

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

September 1, 2006

Primary Completion (ANTICIPATED)

December 1, 2009

Study Registration Dates

First Submitted

September 20, 2007

First Submitted That Met QC Criteria

September 20, 2007

First Posted (ESTIMATE)

September 24, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

August 26, 2013

Last Update Submitted That Met QC Criteria

August 23, 2013

Last Verified

March 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000557417
  • MEX-INC-INCAN-CC-09506

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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