| Inclusion Criteria: | 1) Phase I: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies. Disease may be measurable or non-measurable as per RECIST version 1.1.
2) ECOG performance status 0-2
3) For patients on full-dose low-molecular weight anticoagulation, no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or know varices) is allowed.
4) Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory (ULN)
5) Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels </= 2.5 x ULN and </= 5 x ULN in patients with liver metastases
6) Serum creatinine levels </= 1.5 x ULN
7) Absolute neutrophil count of >/=1,500/mm^3 (ie, >/=1.5 x 10^9/L by International Units [IU]).
8) Platelet count >/=100,000/mm^3 (IU: ≥100 x 10^9/L).
9) Hemoglobin value of >/=9.0 g/dL.
10) No limit to number of prior therapies.
11) Women of childbearing potential must have a negative serum pregnancy test and must be advised to avoid becoming pregnant. Men should be advised to not father a child while receiving treatment. Sexually active women of childbearing potential and men must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized.
12) Patient must be refractory to treatment with 5-FU (either intravenous 5-FU or as the oral prodrug, capecitabine) and oxaliplatin, defined as previous clinical or radiographic progression on or within 3 months of treatment with 5-FU and oxaliplatin. There is no limit to the number of prior lines of therapy.
13) Phase II: Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with measurable metastatic disease documented on diagnostic imaging studies by RECIST version 1.1 criteria
14) Phase II: Patient must be known to have CpG island methylator phenotype. |