Trastuzumab and Capecitabine in Treating Women With Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Phase II Study of Trastuzumab (Herceptin) and Capecitabine (Xeloda) in Women With Taxanes and Anthracyclines Refractory Metastatic Breast Cancer and HER2 Over-Expression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00107393
• Other study ID #: TUGSM-UHA-BC03-01
• Secondary ID: CDR0000380787
• Status: Completed
• Phase: Phase 2
• First received: April 5, 2005
• Last updated: July 9, 2013
• Start date: June 2003
• Est. completion date: November 2008

Study information

• Verified date: October 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving trastuzumab together with capecitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving trastuzumab together with capecitabine works in treating women with metastatic breast cancer.

Description:

OBJECTIVES:

Primary

• Determine the median survival time and 2-year survival rate in women with taxane- and anthracycline-refractory HER2/neu-overexpressing metastatic breast cancer treated with trastuzumab (Herceptin®) and capecitabine.

Secondary

• Determine the progression-free survival of patients treated with this regimen.

• Determine the response rate in patients treated with this regimen.

• Determine the clinical benefit rate of this regimen in these patients.

• Determine the safety profile of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment with trastuzumab (Herceptin®) (yes vs no), HER2/neu status (3+ by immunohistochemistry vs positive by fluorescence in situ hybridization), and class of refractory disease (primary vs secondary vs treatment discontinuation due to adverse events).

Patients receive oral capecitabine once daily on days 1-21 and trastuzumab IV on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for up to 2 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: November 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 75 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

• Metastatic disease

• Patients with only bone metastases are not eligible

• Refractory disease, defined as disease progression, drug-related adverse reaction, or disease relapse during or within 12 months after completion of paclitaxel or docetaxel AND doxorubicin or epirubicin administered in the neoadjuvant, adjuvant, or metastatic setting

• Total neoadjuvant or adjuvant taxane dose > 700 mg/m^2 for paclitaxel or > 240 mg/m^2 for docetaxel

• Total taxane dose > 350 mg/m^2 for paclitaxel or > 120 mg/m^2 for docetaxel in the metastatic setting

• Total neoadjuvant or adjuvant anthracycline dose > 240 mg/m^2 for doxorubicin or epirubicin

• Total anthracycline dose > 120 mg/m^2 for doxorubicin or epirubicin in the metastatic setting

• HER2/neu overexpression

• 3+ by immunohistochemistry or positive by fluorescence in situ hybridization

• No symptomatic brain metastases

• No pleural or pericardial effusion or ascites

• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 20 to 75

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9.0 g/dL

Hepatic

• SGOT or SGPT = 2.0 times upper limit of normal (ULN) (< 3.0 times ULN for patients with liver metastases)

• Alkaline phosphatase = 2.5 times ULN

• Bilirubin = 1.5 mg/dL

Renal

• Creatinine = 1.2 mg/dL

Cardiovascular

• LVEF > 50%

Pulmonary

• No interstitial pneumonia with pulmonary fibrosis

Other

• No history of hypersensitivity reactions

• No serious, uncontrolled infection

• No other malignancy

• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior trastuzumab (Herceptin®) for metastatic disease allowed

Chemotherapy

• See Disease Characteristics

• No prior capecitabine

• At least 2 weeks since prior antimetabolites for metastatic disease

• At least 4 weeks since prior alkylating agents, carcinostatic antibiotics, or other carcinostatic agents

Endocrine therapy

• At least 4 weeks since prior goserelin or leuprolide for metastatic disease

• At least 2 weeks since prior oral endocrine agents for metastatic disease

• No concurrent endocrine therapy

Radiotherapy

• No prior radiotherapy to target lesions

• At least 4 weeks since prior radiotherapy

• No concurrent radiotherapy, including radiotherapy for brain metastases

Surgery

• Not specified

Other

• Concurrent bisphosphonates for bone metastases allowed

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• capecitabine

Locations

Country	Name	City	State
Japan	Kitakyushu Municipal Medical Center	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	Hokkaido Cancer Center	Hokkaido
Japan	Saint Marianna University School of Medicine	Kanagawa
Japan	National Hospital Organization - Osaka National Hospital	Osaka
Japan	Osaka Kosei Nenkin Hospital	Osaka
Japan	Osaka University Graduate School of Medicine	Osaka
Japan	Tohoku University Graduate School of Medicine	Sendai
Japan	St. Luke's International Hospital	Tokyo
Japan	Sakata Municipal Hospital	Yamagata

Sponsors (1)

Lead Sponsor	Collaborator
Tohoku University

Country where clinical trial is conducted

Japan, 

References & Publications (1)

Ishida T, Kiba T, Takeda M, Matsuyama K, Teramukai S, Ishiwata R, Masuda N, Takatsuka Y, Noguchi S, Ishioka C, Fukushima M, Ohuchi N. Phase II study of capecitabine and trastuzumab combination chemotherapy in patients with HER2 overexpressing metastatic b — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median survival and 2-year survival rate as measured by the Kaplan-Meier method 2 years after completion of study treatment			No
Secondary	Progression-free survival			No
Secondary	Response rate			No
Secondary	Clinical benefit rate as measured by Kaplan-Meier method 2 years after completion of study treatment			No
Secondary	Safety profile as measured by the Kaplan-Meier method 2 years after completion of study treatment			Yes