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

NCT ID: NCT02368860

Last Updated: 2021-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-17
• Study Completion Date: 2020-05-21

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OXIRI

OXIRI regimen: oxaliplatin, irinotecan, capecitabine

Group Type: EXPERIMENTAL

oxaliplatin, irinotecan, capecitabine

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Eloxatin, Camptosar, CPT-11, Xeloda

Eligibility Criteria

Inclusion Criteria

1. Patients between 21 to 75 years of age

2. A histopathologically or cytological confirmed diagnosis of locally advanced and/or metastatic PDAC that is unresectable

3. Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) ver 1.1 criteria

4. Life expectancy of at least 12 weeks

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

6. Adequate hematologic function (neutrophils count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L)

7. Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN

8. Adequate renal function (calculated creatinine clearance > 50 mL/min)

9. Able to give informed consent

10. Toxicity related to previous radiotherapy or chemotherapy resolved to ≤ Grade 1

Exclusion Criteria

1. History of prior malignancy except non-melanoma skin cancer within the last 5yrs

2. Uncontrolled central nervous system (CNS) metastases or carcinomatous meningitis

3. Uncontrolled concomitant medical illnesses (e.g. hypertension, myocardial infarct, heart failure, ventricular arrhythmia, diabetes, severe infection)

4. Major surgery within four weeks prior to study treatment

5. Patients on chronic immunosuppressive therapy

6. Pregnant or breast-feeding female patients

7. On anticoagulant therapy with vitamin K antagonists.

8. 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

9. Dose-expansion cohort:

• Previous chemotherapy or radiotherapy

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical Research Council (NMRC), Singapore

OTHER_GOV

Sponsor Role: collaborator

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew CH Ng, Dr

Role: PRINCIPAL_INVESTIGATOR

National Cancer Centre, Singapore

Locations

National Cancer Centre

Singapore, , Singapore

Countries

Singapore

Other Identifiers

NCC-13-01

Identifier Type: -

Identifier Source: org_study_id