- To assess the proportion of confirmed tumor responses in patients with HER2-negative metastatic breast cancer treated with pixantrone dimaleate.
- To describe the distribution of progression-free survival (PFS) times of patients treated with this drug.
- To assess the 6-month PFS rate in patients treated with this drug.
- To describe the overall survival of patients treated with this drug.
- To assess the adverse event profile of this drug in these patients.
- To evaluate the quality of life and patient-reported symptoms of patients treated with this drug.
- To evaluate quantitative and qualitative changes of circulating tumor cells after pixantrone dimaleate therapy. (Correlative study)
- To bank blood and tissue samples for future evaluation of pharmacogenetic and/or proteomic markers. (Correlative study)
OUTLINE: This is a multicenter study. Patients are randomized according to prior doxorubicin treatment ( yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive pixantrone dimaleate IV over 1 hour on day 1. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive pixantrone dimaleate IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo blood sample collection at baseline and periodically during study for circulating tumor cells analysis by CellSearch System and mRNA isolation assays.
Patients complete quality-of-life questionnaires using the Linear Analogue Self Assessment (LASA6) and the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) at baseline and periodically during study.
After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.
- 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
- 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
Last updated: 06/19/2012