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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
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.
National Cancer Centre, Singapore
Singapore, Singapore
RECRUITINGOverall Response Rate (ORR).
The proportion of patients who have a partial or complete response as specified in RECIST 1.1.
Time frame: Up to 3 years.
Clinical Benefit Rate (CBR).
The percentage of advanced cancer patients who achieve complete response, partial response, or at least six months of stable disease as specified in RECIST 1.1.
Time frame: Up to 3 years.
The Grade 3-5 Toxicity Rate.
The proportion of patients who have adverse event(s) with Grade 3-5 toxicity as defined in CTCAE 5.0.
Time frame: Up to 3 years.
Maximum plasma concentration [(Cmax)] of low dose Capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine [DFCR] and 5'- deoxy-5-fluorouridine [DFUR]) and 5FU.
Maximum plasma concentration \[(Cmax)\] of low dose capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine \[DFCR\] and 5'- deoxy-5-fluorouridine \[DFUR\]) and 5FU at Cycle 1 Day 1.
Time frame: At predose, 1 hr, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days)
Trough concentration of low dose capecitabine and its intermediary metabolites and 5FU.
Trough concentration of low dose capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine \[DFCR\] and 5'- deoxy-5-fluorouridine \[DFUR\]) and 5FU.
Time frame: At predose of Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 21 days)
Immunophenotyping from extracted peripheral blood mononuclear cells (PBMCs) - measurement of cytokine and chemokine concentrations in picograms per milliliters using multiplex flow cytometry.
Immunophenotyping from extracted peripheral blood mononuclear cells (PBMCs) - measurement of cytokine and chemokine concentrations in picograms per milliliters using multiplex flow cytometry at these time-points: at predose, end of oxaliplatin infusion, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days); at predose of Cycle 2 Day 1 and at disease progression (up to three years).
Time frame: Up to 3 years.
Genomic analysis of circulating tumour DNA (ctDNA).
Genomic analysis of circulating tumour DNA (ctDNA) from whole blood at these time-points: at predose of every two cycles (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, etc - each cycle is 21 days) and at disease progression (up to three years).
Time frame: Up to 3 years.
Identification of exosomal proteins secreted by extracellular vesicles from plasma.
Identification of exosomal proteins secreted by extracellular vesicles from plasma using mass spectrometry, at the following time-points: at predose, end of oxaliplatin infusion, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days); at predose of Cycle 2 Day 1 and at disease progression (up to three years).
Time frame: Up to 3 years.
Progression-free survival (PFS).
Time from first dose of treatment to disease progression or death, whichever comes first.
Time frame: Up to 3 years.
Overall survival (OS).
Time from first dose to death.
Time frame: Up to 3 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.