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

NCT05929885 | Recruiting Phase 2

• 1 other identifier: LDOXIRI-PDAC-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Pancreatic Cancer

Keywords

Low Dose OXIRI (LDOXIRI); Pancreatic Cancer; Irinotecan; Oxaliplatin; Capecitabine; Pharmacokinetics; Metronomic Chemotherapy; UGT1A1

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR).

  The proportion of patients who have a partial or complete response as specified in RECIST 1.1.

  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.

  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.

  Up to 3 years.

Secondary Outcomes (7)

• 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 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.

  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.

  Up to 3 years.

• Genomic analysis of circulating tumour DNA (ctDNA).

  Up to 3 years.

• Identification of exosomal proteins secreted by extracellular vesicles from plasma.

  Up to 3 years.

Study Arms (1)

Low Dose OXIRI (LD-OXIRI)

EXPERIMENTAL

Low Dose OXIRI (LD-OXIRI) regimen comprises Metronomic Oxaliplatin (O) and Metronomic Capecitabine (xeloda; X) in combination with UGT1A1-directed dosing of Irinotecan (IRI).

Drug: Low Dose OXIRI (LD-OXIRI)

Interventions

Low Dose OXIRI (LD-OXIRI) DRUG

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.

Low Dose OXIRI (LD-OXIRI)

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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),
• Able to provide written and informed consent

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• National Medical Research Council (NMRC), Singapore: collaborator

Study Sites (1)

National Cancer Centre, Singapore

Singapore, 168583, Singapore

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Dr Joycelyn LEE, MBBS, MRCP (UK), M Med

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Joycelyn LEE, MBBS, MRCP (UK), M Med

CONTACT

+65 64368000; joycelyn.lee.j.x@singhealth.com.sg

Tze Wei LIM

CONTACT

+65 64368000; lim.tze.wei@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 43 patients will be enrolled in two stages - In stage 1, a total of 19 patients will be recruited and evaluated for response and toxicity. In stage 2, another 24 patients will be recruited for further evaluation of response and toxicity. Up to 7 patients will be recruited to account for any drop outs (i.e. up to total of 50 patients).

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: July 3, 2023
• Study Start: August 30, 2023
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: June 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)