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

NCT02368860 | Completed Phase 1

• 1 other identifier: NCC-13-01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

  cycle 1 day 1

• Pharmacokinetics analysis of Irinotecan

  cycle 1 day 1

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

  3 years

Other Outcomes (1)

• Circulating tumour cells (CTCs) analysis

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

Study Arms (1)

OXIRI

EXPERIMENTAL

OXIRI regimen: oxaliplatin, irinotecan, capecitabine

Drug: oxaliplatin, irinotecan, capecitabine

Interventions

oxaliplatin, irinotecan, capecitabine DRUG

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

Also known as: Eloxatin, Camptosar, CPT-11, Xeloda

OXIRI

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Cancer Centre

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Oxaliplatin; Irinotecan; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Matthew CH Ng, Dr

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 23, 2015
• Study Start: September 17, 2013
• Primary Completion: May 21, 2020
• Study Completion: May 21, 2020
• Last Updated: June 1, 2021

Record last verified: 2021-05

Locations

SG (1)