Randomized Phase II Study of Two Doses of Pixantrone in Patients With Metastatic Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the breast

- Metastatic disease

- Must have been treated in neoadjuvant, adjuvant, or metastatic setting with
anthracycline and/or taxane

- Must have received 2-3 prior chemotherapy regimens

- Received ≤ 2 prior chemotherapy regimens in the metastatic setting if no prior
neoadjuvant or adjuvant chemotherapy

- Received ≥ 1 prior chemotherapy regimen in the metastatic setting if prior
neoadjuvant or adjuvant chemotherapy

- Measurable disease

- HER2-negative disease

- No active brain metastasis, including leptomeningeal involvement

- CNS metastasis controlled by prior surgery and/or radiotherapy allowed

- There must be ≥ 2 months of no symptoms or evidence of progression

- Patient must discontinue corticosteroid to control brain edema

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Menopausal status not specified

- ECOG performance status 0-2

- Life expectancy > 3 months

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 5 times ULN

- Serum creatinine ≤ 1.5 times ULN

- Negative pregnancy test

- Not pregnant or nursing

- Fertile patients must use effective contraception

- LVEF ≥ 50% and EKG normal within the past 22 days

- No other prior stage III or IV invasive cancer within the past 3 years except
curatively treated nonmelanoma skin cancer

- No uncontrolled hypertension (BP > 160/90 mm Hg on ≥ 2 occasions)

- Patients on any stable new regimen or adjusted anti-hypertensive medications
allowed provided BP < 140/90 mmHg for ≥ 3 different observations in ≥ 14 days

- No clinically significant cardiovascular or cerebrovascular disease, including any
history of the following:

- Myocardial infarction

- Unstable angina pectoris

- NYHA class II-IV congestive heart failure

- Uncontrolled or clinically significant cardiac arrhythmia

- Controlled atrial fibrillation allowed

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Psychiatric illness and/or social situations that would limit compliance with
study requirements

- No co-morbid systemic illnesses or other severe concurrent disease that, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed drug

- No history of allergy or hypersensitivity to drug product excipients or agents
chemically similar to pixantrone dimaleate

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 3 prior chemotherapy regimens for breast cancer

- This number includes neoadjuvant or adjuvant chemotherapy, if given

- If neoadjuvant or adjuvant chemotherapy has been giving it counts as 1 regimen

- Unlimited prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting
allowed

- Lifetime cumulative treatment with doxorubicin ≤ 400 mg/m²

- More than 3 weeks since prior major surgery, chemotherapy, or immunologic therapy

- At least 4 weeks since prior bevacizumab

- No prior radiotherapy within the past 4 weeks and recovered

- Radiotherapy to non-target lesions allowed

- Prior radiotherapy to a target lesion allowed provided there has been clear
progression of the lesion since completion of radiotherapy

- Palliative single dose of radiotherapy allowed

- No other concurrent chemotherapy, biologic agents, or radiotherapy

- No concurrent investigational procedures or investigational therapies

- Trials related to symptom management that do not employ hormonal treatments or
treatments that may block the path of the targeted agents used in this trial may
be allowed