TKM 080301 for Primary or Secondary Liver Cancer

-INCLUSION CRITERIA:

1. Histologically or cytologically confirmed colorectal, pancreas, gastric, breast, ovarian and esophageal cancers with hepatic metastases, or primary liver cancers (Hepatocellular carcinoma and Cholangiocarcinoma).
2. Hepatic disease must be measurable per RECIST Criteria (version 1.1).

3. Hepatic disease should be deemed unresectable as per standard of care criteria.

   Note: Evidence of limited unresectable extrahepatic disease on preoperative radiological studies is acceptable if the life-limiting component of progressive disease is in the liver.

4. All patients must have failed to respond to standard regimens or therapies known to provide clinical benefit. For example:

   - Patients with metastatic colorectal cancer must have received 5-FU and

   leucovorin in combination with either oxaliplatin and/or irinotecan, since level

   1 evidence support increase survival with these regimens, compared to 5-FU and leucovorin alone.

   - Patients with hepatocellular carcinoma must have received sorafenib, since level 1 evidence support increase survival.

5. Greater than or equal to 18 years of age
6. Must be able to understand and sign the Informed Consent Document
7. Clinical performance status of ECOG less than or equal to 2
8. Life expectancy of greater/equal than two months
9. Patients of both genders must be willing to practice birth control during and for four months after receiving chemotherapy

10. Hematology:

    • Absolute neutrophil count greater than or equal to 1500/mm(3) without the support of filgrastim.
    • Platelet count greater than or equal to 100,000/mm(3).
    • Hemoglobin greater than or equal to 9.0 g/dl.

11. Chemistry:

    • Serum ALT/AST less than or equal to 2.5 times the upper limit of normal.
    • Serum Albumin greater than or equal to 3.0 g/dL
    • Serum creatinine less than or equal to 1.5 times ULN unless the measured

    creatinine clearance is greater than 60 mL/min/1.73 m(2)

    - Total bilirubin less than or equal to 1.2 mg/dl

12. International Normalized Ratio (INR) less than or equal to 1.5
13. Seronegative for HIV antibody
14. No chemotherapy or any other investigational drugs within 4 weeks of treatment
15. LVEF greater than or equal to 50 percent
16. QT/QTc interval less than 450 ms

EXCLUSION CRITERIA:

1. Any known brain metastases (prior or current regardless of treatment status)
2. Women of child-bearing potential who are pregnant or breastfeeding, because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
3. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune systems, recent myocardial infarction or heart failure (within 6 months of enrollment).
4. NYHA greater than or equal to 2
5. Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies
6. Weight less than 40 kg
7. Significant ascites, greater than 1000cc in the absence of peritoneal disease
8. Concomitant medical problems that would place the patient at an unacceptable risk for the procedure/drug
9. Patient has known hypersensitivity or previous severe reactions to oligonucleotideor lipid-based products, including liposomal drug products (e.g. Doxil) and phospholipid-based products (parenteral nutrition, Intralipid)
10. Discretion of the PI