Trastuzumab for 6 Months or 1 Year in Treating Women With Nonmetastatic Breast Cancer That Can Be Removed By Surgery

National Cancer Institute, France

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Procedure: adjuvant therapy; Genetic: polymorphism analysis; Biological: trastuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT00381901

INCA-RECF0146

CDR0000509793

INCA-PHARE

EUDRACT-2006-000070-67

Details and patient eligibility

About

RATIONALE: 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. It is not yet known whether giving trastuzumab for 6 months is as effective as giving trastuzumab for 1 year in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying trastuzumab to see how well it works when given for 6 months compared to 12 months in treating women with nonmetastatic breast cancer that can be removed by surgery.

Full description

OBJECTIVES:

Primary

• Compare the disease-free survival of women with nonmetastatic, resectable breast cancer treated with adjuvant trastuzumab (Herceptin®) for 6 months vs 12 months.

Secondary

• Compare cardiotoxicity in patients receiving these regimens.
• Compare the cardiotoxicity and disease-free survival of patients receiving concurrent trastuzumab and chemotherapy vs sequential administration.
• Correlate HER-2 polymorphism with disease-free survival/cardiotoxicity in these patients.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, modality of adjuvant chemotherapy (concurrent vs sequential), and adjuvant hormonal therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I (control arm, 12-month therapy): Patients continue to receive trastuzumab (Herceptin®) IV until a total of 12 months of therapy is completed in the absence of disease progression or unacceptable toxicity.
• Arm II (experimental arm, 6-month therapy): Patients continue to receive trastuzumab* IV until a total of 6 months of therapy is completed in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients who have already finished 6 months of trastuzumab at randomization do not receive further trastuzumab.

Some patients undergo blood collection for HER-2 polymorphism analysis.

After completion of study therapy, patients are followed periodically for approximately 5 years.

PROJECTED ACCRUAL: A total of 7,000 patients will be accrued for this study.

Enrollment: 3,400 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

• Nonmetastatic disease

  • Positive or negative axillary nodes
  • Tumor size ≥ 10 mm

• Resectable disease

• Must have received ≥ 4 courses of chemotherapy for this disease

• A 12-month adjuvant treatment with trastuzumab (Herceptin®) has been initiated

  • Informed consent form must be signed between the third and sixth months of trastuzumab therapy

• Overexpression of HER-2 in the invasive component of the primary tumor as indicated by 1 of the following:

  • 3+ by immunohistochemistry (IHC)
  • 2+ by IHC and confirmation by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female

• Menopausal status not specified

• LVEF considered favorable for continuing trastuzumab treatment as measured by echocardiography or MUGA at 2-4 months after beginning adjuvant trastuzumab

• No serious cardiac illness or medical condition precluding trastuzumab treatment, including any of the following:

  • History of documented congestive heart failure
  • High-risk uncontrolled arrhythmias
  • Angina pectoris requiring antianginal medication
  • Severe dyspnea at rest or oxygen-dependent

• No known hypersensitivity to trastuzumab, murine proteins, or any of the excipients

• Not pregnant or nursing

• No social, geographical, or psychological condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Other prior anti-HER-2 therapy allowed
• No prior trastuzumab other than initiation of trastuzumab adjuvant therapy