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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2008 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00533936
First received: September 20, 2007
Last updated: August 23, 2013
Last verified: March 2008
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: fluorouracil
Drug: paclitaxel
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adjuvant Trastuzumab vs Observation in Locally Advanced Breast Cancer Treated With Neoadjuvant Trastuzumab

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of pathological responses [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival at 3 years [ Designated as safety issue: No ]
  • Cardiac toxicity [ Designated as safety issue: Yes ]
  • Percentage of patients that become negative on the fluorescence in situ hybridization (FISH) test at the end of neoadjuvant therapy [ Designated as safety issue: No ]

Estimated Enrollment: 160
Study Start Date: September 2006
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00533936

Locations
Mexico
Hospital General de Mexico Recruiting
Mexico City, Distrito Federal, Mexico, C.P. 06726
Contact: Contact Person    52-55-5999-6133      
Instituto Nacional de Cancerologia Recruiting
Mexico City, Distrito Federal, Mexico, 14000
Contact: Claudia Arce-Salinas, MD    52-55-5628-0400      
Sponsors and Collaborators
Instituto Nacional de Cancerologia, Columbia
Investigators
Principal Investigator: Claudia Arce-Salinas, MD Instituto Nacional de Cancerologia, Columbia
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00533936     History of Changes
Other Study ID Numbers: CDR0000557417, MEX-INC-INCAN-CC-09506
Study First Received: September 20, 2007
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Trastuzumab
Doxorubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 22, 2014