Metronomic Capecitabine, Oxaliplatin and UGT1A1 Genotype-directed Irinotecan in Metastatic Pancreatic Cancer Patients

Inclusion Criteria:

The patient must meet all of the inclusion criteria to participate in the study.

1. Aged above 21

2. Histopathological diagnosis of pancreatic cancer

3. Advanced disease not amenable to curative resection (locally advanced or metastaticdisease)

4. Measureable disease by RECIST 1.1 criteria

5. Life expectancy of at least 12 weeks

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

7. Adequate hematologic function (granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L),

8. Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal [ULN],AST and ALT, ALP ≤ 3 x ULN or < 5 x ULN in case of hepatic involvement),

9. Adequate renal function (creatinine clearance > 50 mL/min) will be eligible forinclusion into the study.

10. Able to provide written and informed consent

Exclusion Criteria:

Any patient meeting any of the exclusion criteria at baseline will be excluded from participation.

1. History of another malignancy within 5 years prior to registration. Patients with apast history of adequately treated carcinoma-in-situ, basal cell carcinoma of theskin, squamous cell carcinoma of the skin, and superficial transitional cellcarcinoma of the bladder are eligible. Patients with a history of other malignanciesare eligible if they have been continuously disease free after definitive primarytreatment for at least 5 years.

2. Untreated CNS metastases or leptomeningeal disease. Patients with brain metastasesthat have been treated, and are asymptomatic, and have been stable for 3 or moremonths after treatment are allowed. A baseline CT or MRI brain is only required ifthere is clinical suspicion of CNS involvement.

3. Concurrent illness, including severe infection, that may jeopardise the ability ofthe patient to undergo the procedures outlined in this protocol with reasonablesafety

4. Serious medical or psychiatric conditions that might limit the ability of thepatient to comply with the protocol

5. Treatment with palliative chemotherapy or radiotherapy within 4 weeks prior toenrolment into the study

6. Major surgery within two weeks prior to enrolment into the study

7. Patients on chronic immunosuppressive therapy

8. Pregnancy, lactation or inadequate contraception. Women of childbearing potentialmust have a negative pregnancy test within 3 days of enrolment and agree to use areliable means of contraception. Men must have been surgically sterilised or agreeto use a barrier method of contraception

9. Patients on anticoagulant therapy with vitamin K antagonists.