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 I/II trial to study the effectiveness of liposomal doxorubicin and trastuzumab in treating women who have locally advanced , inflammatory, or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer inflammatory breast cancer stage IV breast cancer recurrent breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: antibody therapy  Drug: doxorubicin HCl liposome  Drug: trastuzumab	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the safety, especially the cardiac safety, of doxorubicin HCl liposome and trastuzumab (Herceptin) as first- or second-line therapy in women with metastatic, inflammatory, or locally advanced breast cancer.

PROTOCOL OUTLINE: Patients are stratified according to prior anthracycline therapy (yes vs no). Patients receive doxorubicin HCl liposome IV over 1 hour followed 30 minutes later by trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15. Treatment continues every 21 days in the absence of unacceptable toxicity or disease progression. Patients are followed for at least 3 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed locally advanced, inflammatory, or metastatic adenocarcinoma of the breast that has been treated with no more than 1 prior systemic cytotoxic regimen
• Overexpression of HER2 protein (2+ or 3+)
• Evaluable disease
• History of brain metastases allowed if off steroids and asymptomatic, with a 3 month or greater interval since last dose of brain irradiation, and no evidence of progression
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

Biologic therapy: Prior trastuzumab (Herceptin) allowed

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior antineoplastic therapy
• No more than 1 prior systemic cytotoxic regimen for locally advanced, metastatic, or inflammatory breast cancer
• No prior anthracyclines greater than 240 mg/m2
• No other concurrent antineoplastic agents
• No concurrent treatment with other liposomal products other than doxorubicin HCl liposome

Endocrine therapy:

• See Disease Characteristics
• At least 3 weeks since prior hormonal agents
• No concurrent hormonal therapy

Radiotherapy: See Disease Characteristics

Surgery: Not specified

Other: At least 3 weeks since other prior investigational drugs

--Patient Characteristics--

Age: 18 and over

Sex: Female

Menopausal status: Not specified

Performance status: ECOG 0-1

Life expectancy: Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 10 g/dL

Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN)

Renal: AST or ALT no greater than 4 times ULN

Cardiovascular:

• Adequate cardiac function
• LVEF at least 50% predicted or lower limit of normal

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent medical or psychological condition that would preclude study compliance
• No history of hypersensitivity to anthracyclines, eggs, or egg products

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Maria Theodoulou,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000067609; MSKCC-99054; NCI-G00-1684; LIPO-D9905
Record last reviewed:  May 2003
Last Updated:  October 13, 2004
Record first received:  March 7, 2000
ClinicalTrials.gov Identifier:  NCT00004925
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08