Liposomal Irinotecan, S-1, and Oxaliplatin in Advanced Pancreatic Adenocarcinoma

NCT04662112 | Completed Phase 1

• 1 other identifier: NASOX
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

In present study, the investigators evaluate the safety and efficacy of OIS-derived NASOX regimen (nal-IRI, S-1, oxaliplatin) in advanced pancreatic cancer. NASOX regimen contains nal-IRI, which has recently been proven effective in pancreatic cancer.

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic adenocarcinoma; Liposomal irinotecan; S-1; Oxaliplatin

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity

  3 weeks

• Objective response rates

  Proportion of patients with complete and partial responses defined by RECIST version 1.1

  6 months

Secondary Outcomes (3)

• Overall Survival

  1 year

• Progression-free survival

  1 year

• Adverse events

  1 year

Study Arms (1)

NASOX

EXPERIMENTAL

Liposomal irinotecan+S-1+oxaliplatin

Drug: NASOX

Interventions

NASOX DRUG

Oxalipatin 60 mg/m2 IV (2 h infusion) on Day 1, every 2 weeks Nal-IRI 50-60 mg/m2 IV (FBE, 90 min infusion) on Day 1, every 2 weeks S-1 40mg/m2 oral twice daily on Day 1-7, every 2 weeks

NASOX

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19 years and older
• Histologically or cytologically confirmed, measurable pancreatic adenocarcinoma
• Treatment naïve locally advanced or metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow function as defined by platelets ≥ 100 x 109/L , neutrophils ≥ 1.5 x 109/L and hemoglobin \> 9 g/dL; transfusion is allowed, provided interval is ≥ 7 days prior to screening
• Adequate renal function, with serum creatinine \< 1.5 x upper limit of normal (ULN). And calculated clearance ≥ 50 mL/min/1.73m2 for patients with serum creatinine levels above or below the institutional normal value. Actual body weight should be used for calculating creatinine clearance using the Cockcroft-Gault Equation (CreatClear = Sex x ((140 - Age) / (SerumCreat)) x (Weight / 72); for patients with body mass index (BMI) \>30 kg/m2, lean body weight should be used instead
• Adequate hepatic function with serum total bilirubin ≤ 2 x ULN (biliary drainage is allowed for biliary obstruction), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN is acceptable if liver metastases are present)
• History of any second malignancy in the last 3 years; patients with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years.
• Female patients must be either surgically sterile or postmenopausal, or if of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrolment and agree to use effective barrier contraception during the period of therapy and for one month after the last dose.
• Written, informed consent to the study

You may not qualify if:

• Endocrine or acinar pancreatic carcinoma
• Uncontrolled CNS metastases (Note: Patients who require steroids should be on a stable or decreasing dose to be eligible)
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
• Obstruction of gastrointestinal tract
• Active gastrointestinal bleeding
• Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
• Active infection or an unexplained fever \> 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome
• Use of strong CYP3A4 inhibitors or inducers, or strong UGT1A1 inhibitors (patients are ineligible if unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or strong CYP3A4 inducers at least 2 weeks prior to receiving first dose of irinotecan liposome injection),
• presence of any contraindications for irinotecan, nal-IRI, S1 and Oxaliplatin
• Female patients who are pregnant (positive pregnancy test at screening) or breast-feeding

Sponsors & Collaborators

• Asan Medical Center: lead
• Hallym University Medical Center: collaborator

Study Sites (2)

Hallym University Medical Center

Anyang-si, Gyeonggi-do, 05505, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (4)

• Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.

  PMID: 21561347 BACKGROUND

• Wainberg Z, Boland P, Lieu C, Dayyani F, Macarulla T, Zhang B, Belanger B, Moore Y, Wang T, Maxwell F, Dean A (2019) A phase 1/2, open-label, dose-expansion study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) in patients with previously untreated metastatic pancreatic cancer. Ann Oncol 30 Suppl 4: iv123

  BACKGROUND

• Yoo C, Han B, Kim HS, Kim KP, Kim D, Jeong JH, Lee JL, Kim TW, Kim JH, Choi DR, Ha HI, Seo J, Chang HM, Ryoo BY, Zang DY. Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer. Cancer Res Treat. 2018 Oct;50(4):1324-1330. doi: 10.4143/crt.2017.526. Epub 2018 Jan 8.

  PMID: 29334603 BACKGROUND

• Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-557. doi: 10.1016/S0140-6736(15)00986-1. Epub 2015 Nov 29.

  PMID: 26615328 BACKGROUND

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

• Changhoon Yoo

  Asan Medical Center

  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: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 10, 2020
• Study Start: June 15, 2021
• Primary Completion: October 30, 2023
• Study Completion: December 30, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

KR (2)