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

Sponsored by:	Instituto Nacional de Cancerologia
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00533936

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 II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Cyclophosphamide Fluorouracil Doxorubicin Doxorubicin hydrochloride Paclitaxel Myocet Trastuzumab

U.S. FDA Resources

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

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

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

Locations

Mexico, Distrito Federal
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

Investigators

Principal Investigator:

Claudia Arce-Salinas, MD

Instituto Nacional de Cancerologia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000557417, MEX-INC-INCAN-CC-09506
Study First Received:	September 20, 2007
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00533936 History of Changes
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

Study placed in the following topic categories:

Antimetabolites
Skin Diseases
Immunologic Factors
Adjuvants, Immunologic
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Immunosuppressive Agents
Doxorubicin
Anti-Bacterial Agents

Paclitaxel
Fluorouracil
Tubulin Modulators
Trastuzumab
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Trastuzumab
Alkylating Agents
Breast Diseases
Skin Diseases
Mitosis Modulators

Adjuvants, Immunologic
Breast Neoplasms
Antimitotic Agents
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Neoplasms
Paclitaxel
Fluorouracil
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009