A Phase I, Open-Label, Multicenter, Dose-Escalation Study of the Safety and Pharmacokinetics of a Recombinant Humanized Antibody to Her2 (rhuMAb 2C4) Administered Every 3 Weeks to Subjects With Advanced Solid Malignancies
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