OXIRI [Oxaliplatin (O), Xeloda (X) And Irinotecan (I)] In Pancreatic Adenocarcinoma

Study Overview

OXIRI [Oxaliplatin (O), Xeloda (X) and Irinotecan (I)] in Pancreatic Adenocarcinoma

This is an exploratory Phase I study is to assess the safety and tolerability of the OXIRI regimen [oxaliplatin (O), xeloda (X) and irinotecan (I)] and to evaluate for preliminary evidence of efficacy, in patients with advanced and/or metastatic pancreatic adenocarcinoma. The investigators hypothesize that 2 of 3 weekly doses of oxaliplatin and genotype directed-dosing of irinotecan in combination with chronomodulated capecitabine (xeloda) administered continuously will be more tolerable than the FOLFIRINOX regimen (folinic acid, fluorouracil, irinotecan and oxaliplatin) while maintaining anti-tumour activity.

This study comprises a dose escalation phase using 3+3 design to determine the safety, tolerability and pharmacokinetics of the OXIRI regimen and an expansion phase to further evaluate the MTD and to determine early signs of efficacy. Eligible patients will receive a novel chemotherapeutic regimen (OXIRI regimen) with xeloda being administered in a chronomodulated fashion and the dose of irinotecan being guided by the UGT1A1*28 and UGT1A1*6 genotype status of the patient.

Pancreatic Cancer

DRUG: oxaliplatin, irinotecan, capecitabine

NCC-13-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-01-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-05-28
First Submitted that Met QC Criteria 2015-02-15	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-06-01
First Posted (ACTUAL) 2015-02-23	Results First Posted N/A	Last Verified 2021-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: OXIRI OXIRI regimen: oxaliplatin, irinotecan, capecitabine	DRUG: oxaliplatin, irinotecan, capecitabine fixed doses of intravenous oxaliplatin 50 mg/m2, and intravenous irinotecan administered on days 1 and 8 in a 21 day-cycle while xeloda will be administered daily at around midnight from day 1 to day 14

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: OXIRI

OXIRI regimen: oxaliplatin, irinotecan, capecitabine

DRUG: oxaliplatin, irinotecan, capecitabine

fixed doses of intravenous oxaliplatin 50 mg/m2, and intravenous irinotecan administered on days 1 and 8 in a 21 day-cycle while xeloda will be administered daily at around midnight from day 1 to day 14

Primary Outcome Measures	Measure Description	Time Frame
Safety and tolerability of the OXIRI regimen as measured by the frequency of significant adverse events incurred by the participants, using CTCAE ver. 4 grading system	The safety and tolerability of the regimen will be assessed when the patient is on treatment and till 30 days after treatment.	from first dose to 30 days after last dose

Secondary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose (MTD) of capecitabine when administered in a continuous chronomodulated fashion with genotype-directed dosing of irinotecan and metronomic dosing of oxaliplatin, using a conventional 3+3 design		2 years
Recommended Phase II dose (RP2D) of the OXIRI regimen which is the MTD		2 years
Pharmacokinetics analysis of capecitabine	Plasma level of capecitabine, its intermediary metabolites (5'-deoxy-5-fluorocytidine [DFCR] and 5'- deoxy-5- fluorouridine [DFUR]) and 5FU will be measured at multiple time points on C1D1	cycle 1 day 1
Pharmacokinetics analysis of Irinotecan	Plasma level of Irinotecan, SN-38 (active metabolite of irinotecan) and SN-38G will be measured at multiple time points on C1D1	cycle 1 day 1
Efficacy of OXIRI as measured by response evaluation criteria in solid tumours (RECIST) version 1.1		3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
21 Years

Accepts Healthy Volunteers:

Patients homozygous for uridine diphosphate glucuronosyltransferase (UGT)1A1*6/*6 or UGT1A1*28/*28
Previous oxaliplatin or irinotecan chemotherapy
Treatment with any of the following anti-cancer therapies prior to the first dose of OXIRI within the stated timeframes

Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment. Exception for weekly chemotherapy regimens, where a minimum of 2 week washout from the last dose is required.
Biological therapy (e.g., antibodies) within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks, whichever is shorter, prior to starting study drug
Continuous or intermittent small molecule therapeutics within a period of time that is ≤ 5 t1/2 or ≤ 4 weeks (whichever is shorter) prior to starting study drug
Any other investigational agents within a period of time that is ≤ 5 t1/2 or less than the cycle length used for that treatment or ≤ 4 weeks (whichever is shortest) prior to starting study drug
Wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug 9. Dose-expansion cohort:

Previous chemotherapy or radiotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Medical Research Council (NMRC), Singapore

Investigators

PRINCIPAL_INVESTIGATOR: Matthew CH Ng, Dr, National Cancer Centre, Singapore

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

Patients

Caregivers

Clinical Trial Record