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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00533936
• Other study ID #: CDR0000557417
• Secondary ID: MEX-INC-INCAN-CC
• Status: Recruiting
• Phase: Phase 2
• First received: September 20, 2007
• Last updated: August 23, 2013
• Start date: September 2006

Study information

• Verified date: March 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• fluorouracil

• paclitaxel

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
Mexico	Hospital General de Mexico	Mexico City	Distrito Federal
Mexico	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancerologia, Columbia

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of pathological responses			No
Primary	Disease-free survival			No
Secondary	Overall survival at 3 years			No
Secondary	Cardiac toxicity			Yes
Secondary	Percentage of patients that become negative on the fluorescence in situ hybridization (FISH) test at the end of neoadjuvant therapy			No