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

Eligible patients will be recruited from the National Cancer Centre, Singapore (NCCS). Patients will be referred for assessment by the primary physician to a study investigator for screening. Informed written consent for entry into the trial will be obtained from the patient by a delegated investigator.

All patients eligible for study entry will receive the LD-OXIRI regimen at the National Cancer Centre, Singapore. All concomitant medication taken during the study must be recorded. If a drug is administered prophylactically, this must be noted. The patients will not receive any other investigational drugs while on this study.

There will be a screening period of 28 days, a treatment period till disease progression or unacceptable toxicity, and a post-treatment follow up period of up to 24 months.

Inclusion criteria

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

• Aged above 21
• Histopathological diagnosis of pancreatic cancer
• Advanced disease not amenable to curative resection (locally advanced or metastatic disease)
• Measureable disease by RECIST 1.1 criteria
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate hematologic function (granulocyte count ≥ 1.5 × 10**9/L, platelet count ≥ 100 × 10**9/L),
• 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),
• Adequate renal function (creatinine clearance > 50 mL/min) will be eligible for inclusion into the study.
• Able to provide written and informed consent

Exclusion criteria

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

• History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free after definitive primary treatment for at least 5 years.
• Untreated CNS metastases or leptomeningeal disease. Patients with brain metastases that have been treated, and are asymptomatic, and have been stable for 3 or more months after treatment are allowed. A baseline CT or MRI brain is only required if there is clinical suspicion of CNS involvement.
• Concurrent illness, including severe infection, that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
• Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
• Treatment with palliative chemotherapy or radiotherapy within 4 weeks prior to enrolment into the study
• Major surgery within two weeks prior to enrolment into the study
• Patients on chronic immunosuppressive therapy
• Pregnancy, lactation or inadequate contraception. Women of childbearing potential must have a negative pregnancy test within 3 days of enrolment and agree to use a reliable means of contraception. Men must have been surgically sterilised or agree to use a barrier method of contraception
• Patients on anticoagulant therapy with vitamin K antagonists.