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

Primary Purpose

Pancreatic Cancer

Status

Completed

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

oxaliplatin, irinotecan, capecitabine

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients between 21 to 75 years of age
A histopathologically or cytological confirmed diagnosis of locally advanced and/or metastatic PDAC that is unresectable
Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 criteria
Life expectancy of at least 12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Adequate hematologic function (neutrophils count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L)
Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
Adequate renal function (calculated creatinine clearance > 50 mL/min)
Able to give informed consent
Toxicity related to previous radiotherapy or chemotherapy resolved to ≤ Grade 1

Exclusion Criteria:

History of prior malignancy except non-melanoma skin cancer within the last 5yrs
Uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis
Uncontrolled concomitant medical illnesses (e.g. hypertension, myocardial infarct, heart failure, ventricular arrhythmia, diabetes, severe infection)
Major surgery within four weeks prior to study treatment
Patients on chronic immunosuppressive therapy
Pregnant or breast-feeding female patients
On anticoagulant therapy with vitamin K antagonists.
Dose-escalation cohort:
- 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
Dose-expansion cohort:
- Previous chemotherapy or radiotherapy

Sites / Locations

National Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

OXIRI

Arm Description

OXIRI regimen: oxaliplatin, irinotecan, capecitabine

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Recommended Phase II dose (RP2D) of the OXIRI regimen which is the MTD

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

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

Efficacy of OXIRI as measured by response evaluation criteria in solid tumours (RECIST) version 1.1

Full Information

NCT ID

NCT02368860

First Posted

January 29, 2015

Last Updated

May 28, 2021

Sponsor

National Cancer Centre, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore

1. Study Identification

Unique Protocol Identification Number

NCT02368860

Brief Title

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

Acronym

OXIRI

Official Title

Phase I Trial of OXIRI [Oxaliplatin (O), Xeloda (X) and Irinotecan (I)] Treatment in Patients With Advanced and/or Metastatic Pancreatic Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

September 17, 2013 (Actual)

Primary Completion Date

May 21, 2020 (Actual)

Study Completion Date

May 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Centre, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

OXIRI

Arm Type

Experimental

Arm Description

OXIRI regimen: oxaliplatin, irinotecan, capecitabine

Intervention Type

Drug

Intervention Name(s)

oxaliplatin, irinotecan, capecitabine

Other Intervention Name(s)

Eloxatin, Camptosar, CPT-11, Xeloda

Intervention Description

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 Measure Information:

Title

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

Description

The safety and tolerability of the regimen will be assessed when the patient is on treatment and till 30 days after treatment.

Time Frame

from first dose to 30 days after last dose

Secondary Outcome Measure Information:

Title

Time Frame

2 years

Title

Recommended Phase II dose (RP2D) of the OXIRI regimen which is the MTD

Time Frame

2 years

Title

Pharmacokinetics analysis of capecitabine

Description

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

Time Frame

cycle 1 day 1

Title

Pharmacokinetics analysis of Irinotecan

Description

Plasma level of Irinotecan, SN-38 (active metabolite of irinotecan) and SN-38G will be measured at multiple time points on C1D1

Time Frame

cycle 1 day 1

Title

Efficacy of OXIRI as measured by response evaluation criteria in solid tumours (RECIST) version 1.1

Time Frame

3 years

Other Pre-specified Outcome Measures:

Title

Circulating tumour cells (CTCs) analysis

Description

CTC characterization, and the changes of CTCs number and their relationship to changes in serum CA19-9 levels, tumour response on imaging etc. will be analysed.

Time Frame

at pre-treatment, Day 1 of each cycle and during response evaluation by imaging

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients between 21 to 75 years of age A histopathologically or cytological confirmed diagnosis of locally advanced and/or metastatic PDAC that is unresectable Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 criteria Life expectancy of at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Adequate hematologic function (neutrophils count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L) Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN Adequate renal function (calculated creatinine clearance > 50 mL/min) Able to give informed consent Toxicity related to previous radiotherapy or chemotherapy resolved to ≤ Grade 1 Exclusion Criteria: History of prior malignancy except non-melanoma skin cancer within the last 5yrs Uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis Uncontrolled concomitant medical illnesses (e.g. hypertension, myocardial infarct, heart failure, ventricular arrhythmia, diabetes, severe infection) Major surgery within four weeks prior to study treatment Patients on chronic immunosuppressive therapy Pregnant or breast-feeding female patients On anticoagulant therapy with vitamin K antagonists. Dose-escalation cohort: 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 Dose-expansion cohort: Previous chemotherapy or radiotherapy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthew CH Ng, Dr

Organizational Affiliation

National Cancer Centre, Singapore

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Cancer Centre

City

Singapore

ZIP/Postal Code

169610

Country

Singapore

12. IPD Sharing Statement

Learn more about this trial

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

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