A Dose Escalation Study of OMP-59R5 in Subjects With Solid Tumors

Inclusion criteria

• Subjects must have a histologically confirmed malignancy that is metastatic or unresectable for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. In addition, subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.
• Subjects must have received their last chemotherapy, biologic, or investigational therapy at least 4 weeks prior to enrollment, 6 weeks if the last regimen included BCNU or mitomycin C.
• Age >18 years
• ECOG performance status <2 (see Appendix B)
• Life expectancy of more than 3 months
• Subjects must have normal organ and marrow function as defined below:

• Absolute neutrophil count >1000/mL
• Hemoglobin >9.0 g/dL
• Platelets >100,000/mL
• Total bilirubin <1.5 X institutional upper limit of normal (ULN)
• AST (SGOT) and ALT (SGPT) < 3 X institutional ULN (for subjects with hepatic metastases < 5 X institutional ULN)
• PT and PTT within 1.5 X institutional ULN
• Creatinine <1.5 X institutional ULN OR
• Creatinine clearance >60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
• Women of childbearing potential must have had a prior hysterectomy or have a negative serum pregnancy test and be using adequate contraception prior to study entry and must agree to use adequate contraception from study entry through at least 6 months after discontinuation of study drug. Men must also agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and from study entry through at least 6 months after discontinuation of study drug. Should a woman enrolled in the study or a female partner of a man enrolled in the study become pregnant or suspect she is pregnant while participating in this study or within 6 months after discontinuation of study, she should inform the Investigator immediately.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Subjects receiving any other investigational agents
• Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
• History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
• Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women or nursing women
• Subjects with known HIV infection
• Known bleeding disorder or coagulopathy
• Subjects receiving heparin, warfarin, or other similar anticoagulants, except for subjects on low molecular weight heparin for DVT/PE prophylaxis. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• New York Heart Association Classification II, III, or IV
• Subjects with a blood pressure of >140/90 mmHg. The blood pressure must be taken three times 10 minutes apart. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of blood pressure control.
• Subjects with EKG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.
• Subjects with >1 grade 1 diarrhea.