Evaluation of Polychemotherapy With XELOXIRI-3 in Elderly or Frail Patients With Advanced Pancreatic Adenocarcinoma (ALIX)

Evaluation of Polychemotherapy With XELOXIRI-3 in Elderly or Frail Patients With Advanced Pancreatic Adenocarcinoma (ALIX)

Current standard of care for patients with metastatic Pancreatic Ductal AdenoCarcinoma (PDAC) is chemotherapy, preferential regimen being FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). Due to more hematologic (neutropenia) and gastrointestinal toxicities, FOLFIRINOX is only administered in fit patients (age < 75 years, ECOG Performance status 0-1, and bilirubin < 1.5 ULN).

However, elderly or frail patients represent more than half of patients with PDAC and are treated with gemcitabine monochemotherapy. Maintaining more than one drug (polychemotherapy) may improve survival and quality of life in this population.

ALIX is a non-comparative randomized 2:1 phase II study. This study will assess the efficacy and safety of the polychemotherapy with XELOXIRI-3 versus gemcitabine as first-line chemotherapy in elderly or frail patients with locally advanced or metastatic PDAC.

Study Overview

• Status: Terminated
• Conditions: Metastatic Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: XELOXIRI-3; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Angélique Dr VIENOT; Phone Number: +33381479999; Email: a3vienot@chu-besancon.fr
• Study Contact Backup: Name: Marion JACQUIN; Email: m1jacquin@chu-besancon.fr

Study Locations

• France
  • Besancon, France
    • University Hospital of Besancon
  • Montbéliard, France
    • Hôpital Nord Franche-Comté
  • Mulhouse, France
    • CH Mulhouse
  • Nancy, France
    • CHU Nancy
  • Reims, France
    • CHU Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria :

• Histologically proven pancreatic ductal adenocarcinoma
• Locally Advanced or metastatic disease
• Measurable disease according to RECIST v1.1 criteria
• Age ≥ 75 years;

OR age between 65 and 75 years AND with at least one frailty contraindication to the administration of chemotherapy with FOLFIRINOX:

• Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2
• Total serum bilirubin > 1.5 ULN (biliary drainage allowed)
• Clinico-biological frailty criteria:
• weight loss > 10% in 6 months or > 5% in 1 month
• or body mass index (BMI) ≤ 21
• or serum albumin < 30 g/L

• or ADL (Activities of Daily Living) score < 6

  • Eligible for gemcitabine as first-line chemotherapy
  • Registration in a national health care system
  • Written informed consent obtained from the patient prior to performing any protocol-related procedures

Main Exclusion Criteria:

• Age < 65 years
• Localized non-metastatic cancer
• ECOG-PS 3-4
• Previous treatment For advanced stage (locally advanced or metastatic): chemotherapy, radiochemotherapy; For localized stage: FOLFIRINOX chemotherapy (neoadjuvant or adjuvant); adjuvant chemotherapy with gemcitabine before relapse is permitted (provide it has been administered more than 6 months before)
• Uncontrolled intercurrent cardiovascular disease
• Known or suspected allergy or hypersensitivity to any of the study drugs (capecitabine, oxaliplatin, irinotecan, gemcitabine)
• Bowel obstruction or sub-obstruction or impossible oral treatment
• Prior peripheral neuropathy of grade ≥ 2
• Known complete dihydropyrimidine dehydrogenase (DPD) or UDP-glycosyltransferase 1 polypeptide A1 (UGT1A1) deficiency
• Inadequate hematological, hepatic, and renal functions
• Psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs (Adverse Events) or compromise the ability of the patient to give written informed consent
• Tutelage or guardianship
• Diagnosis of any second malignancy within the last 2 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
• Current participation in another clinical trial using therapeutic experimental agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: XELOXIRI-3; capecitabine 625 mg/m2 twice daily on days 1-7 oxaliplatine 85 mg/m2 on Day 1 irinotecan 90 mg/m2 on Day 3, every 14 days	Drug: XELOXIRI-3; chemotherapy with XELOXIRI-3 regimen; Other Names: Capecitabine; Irinotecan; Oxaliplatine
Active Comparator: Arm B: Gemcitabine; 1000 mg / m2 on D1, D8 and D15, every 28 days	Drug: Gemcitabine; chemotherapy with Gemcitabine regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
6 months Progression-Free Survival (PFS) rate	6 months after the date of initiation of treatment (1st day of 1st cycle of chemotherapy)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Investigators: Principal Investigator: Angélique VIENOT, Dr, University Hospital of Besancon

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2019
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 3, 2019
• First Posted (Actual): June 5, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Irinotecan; Gemcitabine
• Other Study ID Numbers: P/2018/395

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No