Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of breast cancer
• Metastatic disease
• No de novo metastasis
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy > 3 months
• Menopausal status not specified
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Hemoglobin ≥ 9 g/dL
• Creatinine clearance ≥ 50 mL/min
• AST/ALT < 3 times upper limit of the normal (ULN)
• Total bilirubin normal (unless documented history of congenital hypobilirubinemia)
• LVEF normal by ECHO or MUGA scan
• Not pregnant or breastfeeding
• Negative pregnancy test
• Fertile patients must use effective contraception from the time of their negative pregnancy test before treatment, during treatment, and 28 days following treatment
• Able to swallow and retain oral medication
• History of other malignancies (e.g., cervical carcinoma in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin) allowed provided patient has been treated and disease free ≥ 5 years and deemed by the investigator to be at low risk for recurrence
• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib ditosylate or excipients
• No malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
• No active or uncontrolled infection
• No known history of uncontrolled or symptomatic angina, arrhythmias, congestive heart failure, or other cardiac disorders
• No history of prolonged QT interval
• No active hepatic or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• No concurrent disease or condition that would render the patient inappropriate for study participation, or serious medical disorder that would interfere with the patient's safety
• No dementia, altered mental status, or psychiatric condition that would prohibit the understanding or rendering of informed consent

PRIOR CONCURRENT THERAPY:

• Prior radiotherapy for treatment of primary tumor allowed
• Prior non-anthracycline based regimens in neoadjuvant, adjuvant, or metastatic setting allowed
• Prior adjuvant Herceptin® or ErbB inhibitors allowed provided disease progression was > 6 months after completion of treatment
• More than 3 months since prior Herceptin®, ErbB1, or ErbB2
• No prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens
• More than 3 weeks since prior and no concurrent medications that would prolong QT interval
• More than 1 month or 5 half-lives (whichever is longer) since prior, no concurrent investigational drugs
• No unresolved or unstable, serious toxicity from prior investigational drug and/or cancer treatment
• At least 3 weeks since prior and no concurrent prohibited medications (i.e., CYP3A4 inducers or inhibitors)
• No concurrent non-study anticancer therapy (i.e., chemotherapy, immunotherapy, or biologic therapy)
• No concurrent participation in another clinical trial
• No concurrent grapefruit or grapefruit juice
• Concurrent bisphosphonates allowed