TKM 080301 for Primary or Secondary Liver Cancer

BACKGROUND: \- Metastatic liver disease is a life-limiting factor for patients with a variety of cancers. For unresectable liver metastases, the 5-year survival is \< 5%. * For selected histologies the 5-year survival of resectable hepatic metastases ranges from 20-60%, suggesting that control of liver metastases could result in prolonged survival. * Phase I through III trials have shown that Hepatic Arterial Infusion (HAI) is safe. However, agents used thus far in HAI have limited efficacy. * TKM-080301 is a lipid nanoparticle (LNP) formulation containing siRNA against the PLK1 (polo-like kinase-1) gene product. More specifically, TKM-080301 is a type of LNP formulation, referred to as SNALP (Stable Nucleic Acid Lipid Particles). PLK1 has been validated as a molecular target and a prognostic factor in a variety of cancers. Inhibition of PLK1 activity in proliferating cancer cells rapidly induces mitotic arrest and apoptosis. * This study will offer HAI with TKM-080301 to patients with unresectable and/or life threatening primary liver cancer or liver metastases. OBJECTIVES: Primary Objective: \- To evaluate feasibility of administering TKM-080301 via HAI and to characterize the pharmacokinetics (PK) and pharmacodynamics of TKM-080301 administered by HAI. Secondary Objectives: * To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of TKM-080301. * To evaluate response rate using RECIST, PET and EASL criteria. * To evaluate the conversion rate from unresectable to resectable disease. ELIGIBILITY: * Patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases; or primary liver cancer patients who have demonstrated progressive disease following standard of care treatment. * 18 years old or greater with an ECOG 0-2 * Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery or chemotherapy. DESIGN: \- This is a dose escalation phase-I study testing HAI of TKM-080301 for patients with unresectable colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers. * Up to 54 patients who meet eligibility criteria will receive HAI with TKM-080301. * Initial dose will be 4 mg/m(2); treatment will be given every 2 weeks for up to 12 doses. * Patients will be evaluated every 6 weeks. Patients whose tumors become resectable will be offered this option; patients who show progressive disease will be taken off treatment. All patients will be followed for survival.