| Inclusion Criteria: | 1) Patients must have evaluable IBC substantiated by 1) history of invasive breast cancer per biopsy pathology report, 2) current photographs (global view and close-up views of all skin lesions) submitted at screening demonstrating unequivocal evidence of IBC as determined by either the medical monitor alone or in consulation with one or more of the study Principal Investigators. The photographs, along with the completed Inflammatory Breast Cancer Skin Assessment Tool (IBSAT), must be reviewed and approved by GSK before a patient can be randomized.
2) Patients with secondary IBC are eligible.
3) Measurable lesions (cutaneous or radiographic) may be in the field of prior standard or palliative radiation therapy; however, there must be at least a 4 week period between the last radiation treatment and the baseline scan documenting disease status for the lesion to be measurable. If the irradiated lesion is the only site of disease, documented progression of the irradiated lesion is required.
4) Disease progression or relapse following treatment for invasive breast cancer, which must have included a chemotherapy regimen. In regions where trastuzumab is available with no barriers to access*, patients must have received prior trastuzumab in addition to chemotherapy in order to be eligible. (*Barriers to access may include financial considerations).
5) Unequivocal ErbB2 overexpressing 3+ IHC, or 2+ IHC with ErbB2 by FISH/CISH, or ErbB2 by FISH/CISH alone (If not IHC). ErbB2 > 6 ErbB2 gene copies/nucleus for test systems or an ErbB2/CEP 17 ratio of more than 2.2. Sites must submit a copy of lab of ErbB2 overexpression, if testing performed at a local lab, with the screening worksheet. Archived tumor must be provided for all patients for ErbB2 FISH in a central lab. Pts will be on study based on local ErbB2 expression results. If archived tumor is not available, a biopsy must be obtained at screening and sent to TMD Lab for ErbB2 FISH.
6) Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up. Procedures conducted as part of the patients routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
7) Females age =/> 18 years, except in Tunisia. In Tunisia, patients must be ≥ 20 years to be eligible for this study.
8) Adequate organ function: ANC >/= 1.5 X 10^9/L, Hgb >/= 9 g/dL - no transfusion within 7 days of screening. Platelets >/=100 X 10^9/L, INR </= 1.2 X ULN, PTT </=1.2 X ULN, Total bilirubin </=1.5 X ULN (elevation due to Gilberts syndm OK), AST and ALT </= 2.5 X ULN, Serum Creatinine </=1.5 mg/dL, or, if serum creatinine >1.5 mg/dL, calculated creatinine clearance is >/= 50 mL/min, Urine Protein to Creatinine Ratio is <1. If UPC >/= 1, then a 24-hour urine protein must be assessed. Patients must have a 24-hour urine protein value <1g to be eligible.
9) Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive or where MUGA scans are the accepted standard. Patients with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure are not eligible.
10) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
11) A female is eligible to enter and participate in this study if she is of non-childbearing (i.e., physiologically incapable of becoming pregnant) potential, including any female who has had: a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation, is post-menopausal. Patients not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >/= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).
12) Continued from Inclusion # 11. Patients must discontinue HRT prior to study enrollment due to the potential for inhibition of CYP enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. If a female patient is determined not to be post-menopausal, they must use adequate contraception, as defined immediately below.
13) Cont. from Inclusion # 12. Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, has used adequate contraception since the pregnancy test and agrees to use adequate contraception as described below. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
14) Cont. from Inclusion # 13. An intrauterine device with a documented failure rate of less than 1% per year. Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female. Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product. Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
15) Female patients who are lactating should discontinue nursing prior to the first dose of investigational product and should refrain from nursing throughout the treatment period and for 14 days following the last dose of investigational product. |