TACE Plus Axitinib and Hydroxychlorquine for Liver-Dominant Metastatic Colorectal Cancer (CRC)

Who can take part

• Age 18 years or more
• Pathologically-verified diagnosis of colorectal adenocarcinoma
• Measurable metastasis to liver with at least one dimension ≥ 1.0 cm
• Liver dominant metastases as judged by multidisciplinary team consensus review of cross-sectional imaging of the chest, abdomen and pelvis
• At least 2 weeks must have elapsed from the last dose of chemotherapy before starting HCQ and at least 4 weeks must have elapsed from the last dose of VEGF/VEGFR therapy prior to starting axitinib
• Subjects must be at least 2 weeks beyond prior radiotherapy or surgery, and have recovered from all therapy associated toxicities
• Eastern Cooperative Oncology Group (ECOG) Performance status must be 0-1 (see Appendix II)
• Absolute granulocyte count > 1,500/ul, platelet count > 75,000/ul, International Normalized Ratio (INR) < 1.6
• Serum creatinine < 2.0 mg/dl; serum bilirubin < 2.0 mg/dl
• Urine protein:creatinine ratio < 1 or 24-hour urine protein < 1 gm/day
• Liver function Child-Pugh A
• Competent and willing to provide informed consent
• Patients of reproductive potential agree to use approved contraceptive methods per section 5.4

Who cannot take part

• Prior hepatic arterial infusion chemotherapy or hepatic radiation therapy. Prior surgical resection or ablation of liver metastases is acceptable
• No more than two prior lines of systemic chemotherapy
• Contraindications to angiography and selective visceral catheterization:; severe allergy or intolerance to contrast media not controllable with prophylaxis; bleeding diathesis not correctable by usual forms of therapy; severe peripheral vascular disease precluding catheterization
• Known allergic reactions to irinotecan, HCQ or axitinib
• Allergy to contrast not mitigated by usual prophylaxis
• Serious infection requiring intravenous therapy
• Known retinal disease
• Poorly controlled hypertension, defined as a blood pressure > 150/100 at the time of enrollment. Patients with a preexisting hypertension must be on a stable anti-hypertensive regimen
• History of abdominal fistula, gastrointestinal perforation, or serious non-healing wounds, ulcers, or bone fractures
• Known New York Heart Association class II or greater congestive heart failure (defined as symptoms of fatigue, dyspnea, or other symptoms with ordinary physical activity)
• Known untreated brain metastases. History of treated metastases off steroids allowed
• Contraindications to hepatic artery embolization:; high risk of hepatic failure, indicated by the constellation of greater than 50% liver replacement by tumor, lactate dehydrogenase (LDH) >425 mU/ml, aspartate aminotransferase (AST) >100mU/ml. and bilirubin >2 mg/dl; tumor volume >75% of total liver volume; portal vein occlusion without hepatopetal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow; hepatic encephalopathy
• Pregnancy or lactation