| Inclusion Criteria: | Life expectancy of equal to or greater than 12 weeks.
Signed informed consent.
Subjects eligible for cohort A, must have tumors that overexpress ErbB2 defined as +3 by IHC or +2 by IHC and FISH+. The status of ErbB2 expression must be documented prior to study entry.
A female, 18 years or older, is eligible to enter and participate in this study if she is of Non-childbearing potential or is of childbearing potential but agrees to either complete abstinence from intercourse from 2 weeks prior to admin of first dose of GW572016 until 28 days after the final dose or use an acceptable method of birth control. Patients must have a negative serum pregnancy test at screening.
At least 3 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, hormonal therapy for cancer, or surgery (except for minor surgical procedures) before beginning treatment with GW572016, except for trastuzumab which must be discontinued at least 2 wks prior to beginning of study drug. Subjects must have recovered or stabilized sufficiently from side effects associated with prior therapy.
Subjects with stable CNS metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible.
ECOG Performance Status of 0 to 2.
Able to swallow and retain oral medication.
Subjects must complete all screening assessments as outlined in the protocol.
Subject must have aadequate Hepatic function as follows: Albumin equal to or greater than 2.5 g/dL, Serum bilirubin equal to or less than 1.5 x ULN unless due to Gilbert's Syndrome, and AST & ALT equal to or less than 3 x ULN without liver mets and equal to or less than 5 x ULN if documented liver mets.
Subject must have adequate Renal function as follows: Serum Creatinine equal to or less than 1.5 mg/dL, OR Calculate Creatinine Clearance equal to or less than 40 mL/min.
Subjects must have histologically confirmed invasive breast cancer with Stage IIIb or IV disease. If the disease is restricted to a solitary lesion- its neoplastic nature should be confirmed by cytology or histology.
Subjects must have refractory breast cancer defined as progression after prior therapy which must include (see protocol for details).
Documentation of disease progression of the most recent treatment is required. Disease progression for study entry is defined as appearance of any new lesion or increase of 25% or more in one or more existent lesions.
The required radiological scans and/or photographs required from the pt's most recent treatment must document: the baseline or lowest tumor burden (nadir scans) & disease progression.
For skin disease only pts, documentation of the baseline/nadir and disease progression scans will consist of clinical dictation notes that specify: the date of assessment- description of skin lesion(s)- dimensions of lesions(s)- and photographs (if available).
Pts must have archived tumor tissue avail. to re-evaluate intra-tumoral expression levels of ErbB1 and ErbB2 by IHC and FISH testing by study central lab. Central lab. results not used to determine pt elig., unless testing is being used for req?d documentation of ErbB2 overexpression.
Measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors) [Therasse, 2000].
Bisphosphonate therapy for bone metastases is allowed however- TX must be initiated prior to the 1st dose of study therapy. Except for the TX of osteoporosis, prophylactic use of bisphosphonates will not be permitted in subjects without bone disease.
Cardiac ejection fraction within institutional range of normal as measured by echocardiogram or MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconculsive. Copies of Echocardiograms (or MUGA exams) will be required for all pts for review by an independent review committee.
Subject must have adequate Hematologic function as follows: ANC equal to or greater than 1.5 x 10(9)/L, Hemoglobin equal to or greater than 9 g/dL, Platelets equal to or greater than 100 x 10(9)/L. |