RecruitingPhase 2NCT05929885

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

A Phase II Study of Metronomic Capecitabine, Oxaliplatin and UGT1A1 Genotype-directed Irinotecan in Metastatic Pancreatic Cancer Patients.

Sponsor

National Cancer Centre, Singapore

Enrollment

50 participants

Start Date

Aug 30, 2023

Study Type

INTERVENTIONAL

Conditions

Metastatic Pancreatic Cancer

Summary

This is a single-centre, non-randomized, open label phase II trial to be conducted at the National Cancer Centre, Singapore (NCCS). Patients diagnosed with metastatic PDAC will be eligible to enrol. The investigators hypothesize the anticancer activity of low dose OXIRI (LD-OXIRI) regimen comprising of metronomic oxaliplatin (O) and metronomic capecitabine (xeloda; X) in combination with UGT1A1-directed dosing of irinotecan (IRI) to be a tolerable regimen in patients with advanced PDAC and will lead to a favourable response rate. Patients will be prospectively enrolled in two stages - In stage 1, patients will be recruited and evaluated for response and toxicity. In stage 2, more patients will be recruited for further evaluation of response and toxicity.

Eligibility

Min Age: 21 YearsMax Age: 99 Years

Inclusion Criteria10

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 Criteria9

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.

Interventions

DRUGLow Dose OXIRI (LD-OXIRI)

The LD-OXIRI regimen will be administered in the following sequence: * metronomic capecitabine (Xeloda; X) 650mg/m2 will administered twice a day on a daily a continuous basis; * intravenous metronomic oxaliplatin (O) 50 mg/m2 will be infused over 120 minutes on days 1 and 8 of a 21 day-cycle; followed by * intravenous irinotecan (I) will be infused over 90 minutes on days 1 and 8 of a 21 day-cycle. The dose of irinotecan will be based on the particular patient's UGT1A1\*6 and UGT1A1\*28 genotype status.