Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with or without trastuzumab in treating women who have metastatic breast cancer.

Further Study Information

OBJECTIVES:

• Assess the safety, toxicity, and feasibility of doxorubicin hydrochloride (HCL) liposome and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast cancer, particularly with respect to cardiotoxicity.

• Assess the overall objective response rate, response duration, time to treatment failure, and median survival of these patients with these treatment regimens.

• Assess any association between trough plasma levels of cardiac troponin T and brain natriuretic peptide and any cardiac event (congestive heart failure or left ventricular ejection fraction decrease).

OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression status.

• Arm I (HER2 nonoverexpressed): Patients receive doxorubicin hydrochloride liposome IV over 30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

• Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30 minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3 weeks for 8 courses.

Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 89 patients were accrued for this study.

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed metastatic adenocarcinoma of the breast

• HER2 nonoverexpressed (0-1+) OR overexpressed (2-3+)

• Measurable or evaluable disease

• Prior brain metastases responsive to treatment of radiotherapy and/or surgery allowed (cannot be only site of metastases)

• Age 18 and over

• Female

• Fertile women must use effective contraception

• Eastern Cooperative Oncology Group performance status of 0,1,or 2

• The following lab values obtained at least 4 weeks prior to registration: granulocyte count at least 1,500/mm^3, platelet count at least 100,000/mm^3, SGOT no greater than 2.5 times upper limit of normal, bilirubin normal, and creatinine no greater than 1.5 mg/dL

• Left ventricular ejection fraction at least lower limit of normal (LLN)

• Prior adjuvant chemotherapy allowed if completed 6 months before metastasis

• Prior endocrine therapy in either a metastatic or adjuvant setting, but patients must have been off such therapy for at least 2 weeks prior to registration

• Prior radiotherapy allowed only to conserved breast, postmastectomy chest wall with or without internal mammary lymph node chain (IMN), or field containing less than 25% bone marrow

• At least 2 weeks since prior radiotherapy

• At least 2 weeks since surgery (including mastectomy) and recovered

Exclusion Criteria:

• Prior deep venous thrombosis or thromboembolic condition

• Prior myocardial infarction or congestive heart failure

• Arrhythmia requiring medication

• Hypertension or systolic or diastolic dysfunction

• Ventricular hypertrophy or conduction abnormality

• Prior pulmonary thromboembolism

• Other malignancy within the past 5 years except curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin

• Pregnant or nursing

• Prior trastuzumab (Herceptin™)

• Prior chemotherapy for advanced or local/regional recurrent disease

• Prior anthracyclines or anthracenediones

• Prior photon IMN treatment

• Concurrent radiotherapy

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Antonio C. Wolff, MD

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00004888
Information obtained from ClinicalTrials.gov on December 15, 2011

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