A Pharmacodynamic Study of AV-299 (Formerly SCH 900105) in Subjects With Advanced Solid Tumors Who Have Liver Metastases

Inclusion Criteria

• •Ability to give written informed consent and be able to adhere to dose and visit schedules.
• •Diagnosis of an advanced colorectal, breast, gastric/esophageal or pancreatic cancer with liver metastases that are amenable to biopsy.
• •Histological or cytological evidence of malignancy.
• •Advanced metastatic colorectal, breast, gastric/esophageal or pancreatic cancer that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which subject is not a candidate for, or is unwilling to undergo standard therapy.
• •Note: Additional tumor histologies may be eligible based on available HGF/c-Met pathway data and approval by the Sponsor.
• •Disease that is currently not amenable to curative surgical intervention.
• •Male or female and ≥ 18 years of age.
• •ECOG performance status of 0-1.
• •Measurable p-Met by immunohistochemistry in archived or otherwise available tumor sample.
• •Female subjects of childbearing potential must have negative pregnancy test within 5 days prior to first dose of study drug.
• •Female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an effective method of contraception during the study and for 60 days after the last dose of AV-299 (formerly SCH 900105). Examples of effective methods of contraception include oral contraceptives or double barrier methods such as condom plus spermicide or condom plus diaphragm.
• •Adequate hematologic function as evidenced by Hg ≥ 9g/dL, WBC ≥ 3000 per mm3, ANC ≥ 1500 per mm3 and platelet count ≥ 100,000 per mm3.
• •Adequate hepatic function as evidenced by a serum bilirubin level ≤ 1.5 × ULN (except with known Gilbert's Syndrome) and with serum AST/ALT levels ≤ 5 × ULN.
• •Adequate renal function as evidenced by a serum creatinine level ≤ 1.5 × ULN or a calculated creatinine clearance \> 60 mL/min.
• •Adequate coagulation function as evidenced by PTT ≤ 1.5 × ULN and INR ≤ 1.5 × ULN.
• •Recovery from the effects of any prior surgery, radiotherapy, or systemic antineoplastic therapy.
• •Subjects with abnormal liver function tests (LFTs) who have not been screened for Hepatitis B or C within the past 6 months prior to study enrollment, will need to be screened for Hepatitis B and C and can only be enrolled if the screening is negative.