Axitinib Monotherapy With Early Dynamic Contrast Enhanced Ultrasound Monitoring in Chemorefractory Third Line Metastatic Colorectal Cancer

Inclusion Criteria

Patients must meet all of the following inclusion criteria to be eligible for enrolment into the study:

• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastas(es). At least one of which should not have had any focal therapy including radiofrequency ablation, chemoembolization, ethanol or cryoablation.
• Failed at least 2 chemotherapy regimens in advanced disease.
• Evidence of unidimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST).
• 18 years of age or older.
• ECOG performance status of 0 or 1.
• Resolution of all acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade ≤1.
• Adequate organ function as defined by the following criteria:

Serum aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤2.5 x upper limit of normal (ULN). For patients with liver metastases, 450 msec for males and >470 msec for females.

• Hypertension uncontrolled by medication (>150/100 mmHg despite optimal medical therapy).
• On-going treatment with therapeutic doses of warfarin (however, low dose warfarin up to 2mg daily for deep vein thrombosis prophylaxis is allowed). Low molecular weight heparin (LMWH) is allowed.
• Diagnosis of any second malignancy within the last 3 years that is potentially liable to interfere with study outcomes (basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma and hormone controlled locally advanced prostate cancer that has been adequately treated with no evidence of recurrent disease for 12 months, are allowed)
• History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT or MRI scan.
• Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack.
• Known human immunodeficiency virus (HIV) infection.
• Pregnancy, breastfeeding, or unwillingness/inability to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for up to 3 months after discontinuing study drug if of reproductive potential.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgement of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator would make the patient inappropriate for entry into the trial.
• Non-English speaking
• Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• Gastrointestinal abnormalities including: inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection; treatment for active peptic ulcer disease in the past 6 months; active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis or melaena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; malabsorption syndromes
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
• Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phen