Safety Study of rhuMAb 2C4 to Treat Advanced Solid Tumors

Inclusion Criteria:

• Signed informed consent
• Age >=18 years old
• ECOG performance status of 0 or 1 (see Appendix F)
• Life expectancy of >=12 weeks
• Histologically documented, incurable, locally advanced or metastatic solid malignancies
• Disease progression on or after standard effective therapy or a malignancy for which there is no standard therapy
• At least one bi-dimensionally measurable lesion (>=2 cm [>=1 cm on spiral CT scan])
• HER2-negative status as defined by fluorescence in situ hybridization (FISH) testing (only for subjects with breast cancer)
• Use of an effective means of contraception for women of childbearing potential
• Granulocyte count of >=1500/uL, platelet count of >=100,000/uL, and hemoglobin of >=9 g/dL
• Serum bilirubin less than or equal to the upper limit of normal (ULN) and alkaline phosphatase, AST, and ALT <=2.5x ULN (ALT and AST <=5x ULN for subjects with liver metastases; alkaline phosphatase <=5x ULN for subjects with liver or bone metastases)
• Serum creatinine less than or equal to ULN or creatinine clearance of >=60 mL/min
• International normalized ratio (INR) of <1.3 and activated partial thromboplastin time (aPTT) of <1.5x ULN

Exclusion Criteria:

• Pleural effusions, ascites, or bone lesions as the only manifestation of the current cancer
• Symptomatic or untreated brain metastases
• Prior chemotherapy, hormonal therapy (except for androgen-deprivation therapy for subjects with prostate cancer), radiotherapy, or immunotherapy within 4 weeks of Day 1 (within 6 weeks for nitrosoureas or mitomycin)
• Prior treatment with Herceptin
• Prior cumulative doxorubicin dose of >360 mg/m2 or the equivalent
• History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
• History of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication
• Ejection fraction of <50% or below the lower limit of normal determined by ECHO (Subjects who are unable to have ejection fraction evaluated by ECHO may have ejection fraction evaluated by a MUGA scan, although this must be discussed with the Medical Monitor prior to enrollment.)
• Active infection requiring IV antibiotics
• Uncontrolled hypercalcemia (>11.5 mg/dL)
• Clinically important history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Known human immunodeficiency virus (HIV) infection
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications
• Major surgery or significant traumatic injury within 3 weeks of Day 1
• Pregnancy or lactation
• Inability to comply with study and follow-up procedures