Low recruitment

Primary objective:

To determine the brain response rate of Lipo-Dox in breast cancer patients with brain metastasis

Secondary objectives:

1. To determine the overall objective response rate (ORR)
2. To determine the progression free survival, and duration of objective response
3. To evaluate the overall survival (OS)
4. To assess the safety profiles

This is an open-label, non-comparative phase II clinical trial. Approximately thirty-three patients will be enrolled in order to obtain twenty-nine evaluable subjects who received two cycles of study treatment in Simon's 2-stage optimal design.

Duration of subject involvement: Study treatment should be administered up to disease progression, intolerable toxicity, or consent withdrawal.

Recruitment period: 10 months

Inclusion Criteria:

• Histologically or cytologically proved breast cancer
• Relapse/recurrent brain metastasis progression after brain radiotherapy
• Presence of brain measurable disease which is defined as at least one brain lesion that can be measured in at least 1 dimension as ³ 20 mm with magnetic resonance image (MRI)
• Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed
• Performance status of ECOG 0, 1, 2
• With normal left ventricular ejection fraction and normal ventricular contractility
• Age 21 years or older
• Life expectancy equal or longer than 3 months
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior anthracycline-containing chemotherapy with cumulative dose exceed 400mg/m2 doxorubicin or 750 mg/m2 Epirubicin

• Surgery , radiotherapy, hormonal therapy or chemotherapy within 4 weeks prior to entering the study

• Prior liposomal doxorubicin treatment

• Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period

• Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study

• Brain metastases defined as meninges metastases

• Presence of serious concomitant illness which might be aggravated by study medication:

  • Uncontrolled infection (active serious infections that are not controlled by antibiotics)
  • Active cardiac disease e.g. decompensate myocardial infarction within the 6-month period preceding entry into the study.
  • History of ventricular arrhythmia or congestive heart failure.

• Presence of abnormal left ventricular ejection fraction

• Hematopoietic function as defined below:

  • Hemoglobin<10g/dl
  • ANC< 1,500/uL
  • Platelets<100,000/uL

• Organ function as defined below:

  • Total bilirubin >1.5 × ULN
  • ALT / AST>3 × ULN (>5.0 x ULN if hepatic metastasis)
  • Creatinine >1.5 × ULN

• Mental status is not fit for clinical trial

• Pregnant or breast feeding women, or women of child-bearing potential unless using a reliable and appropriate contraceptive method