Neoadjuvant Chemoradiation With Nal-IRI and Capecitabine Guided by UGT1A1 Status in Patients With Rectal Cancer

Exploratory Study on the Efficacy and Safety of Long-course Neoadjuvant Chemoradiation With Liposomal Irinotecan and Capecitabine Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer

This single-arm trial will explore the efficacy and safety of long-course neoadjuvant chemoradiation with liposomal irinotecan and capecitabine guided by UGT1A1 status in patients with locally advanced rectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: liposomal irinotecan; Drug: Capecitabine; Radiation: Radiation threapy

Detailed Description

This is a single-center, single-arm, prospective clinical study. The aim of this study is to explore the short-term and long-term efficacy and safety of total neoadjuvant therapy with irinotecan liposome in patients with locally advanced rectal cancer. Patients' nutritional status, quality of life, changes in symptoms, and adverse events will also be regularly assessed and registered during the implementation phase of the study, and patients will be treated promptly if symptoms are assessed as positive.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Linlin Xiao, Ms.; Phone Number: 18533167355; Email: drxiaolinlin@163.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • Hebei Medical University Fourth Hospital
      • Contact: Fengpeng Wu, Professor; Phone Number: 15032818011

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 18~75 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0~1.
• Histopathologically confirmed rectal adenocarcinoma.
• The lower edge of the primary tumor is located below the peritoneal reflection or located ≤ 10 cm above the anal verge.
• Clinical stage: T3-4NanyM0 or T1-2N+M0.
• Adequate bone marrow function as evidenced by: Absolute neutrophil count (ANC) ≥1.5×10^9/L, Platelet count ≥100×10^9/L, Hemoglobin (Hb) ≥90 g/L.
• Adequate hepatic function as evidenced by: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN, Serum albumin ≥3 g/dL.
• Adequate renal function as evidenced by: Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min.
• Be willing to undergo UGT1A1 gene testing and UGT1A1 genotype of *1*1 or *1*28.
• Accept the neoadjuvant chemoradiotherapy protocol of this study and sign the informed consent.

Exclusion Criteria:

• Any other malignancy within 5 years, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV infection.
• Combined with uncontrollable systemic diseases.
• History of allergy or hypersensitivity to drug or any of their excipients.
• Any clinical indicators indicating contraindications to radiotherapy/chemotherapy and surgery.
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
• Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
• Patients with poor cognitive abilities who are unable to answer questions, fill out questionnaires, or have mental disorders.
• Patients who do not meet the inclusion criteria; patients who meet the inclusion criteria but are not suitable to participate in this trial judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liposomal irinotecan-based TNT therapy; Concurrent Chemoradiotherapy (Radiation 50.4Gy/28 fractions + Capecitabine 625mg/m^2 bid + Liposomal irinotecan 50mg/m^2) followed by 4-6 cycles of Chemotherapy (Capecitabine 1000mg/m^2 bid d1-7 + Liposomal irinotecan 70mg/m^2 or 50mg/m^2, d1, Q2W) before surgery.	Drug: liposomal irinotecan; Liposomal irinotecan: 50mg/m^2 or 70mg/m^2; Other Names: nal-IRI; Drug: Capecitabine; Capecitabine: 625mg/m^2 or 1000mg/m^2 bid.; Other Names: Xeloda; Radiation: Radiation threapy; 50.4Gy/28 fractions; Other Names: RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response	Defined as the proportion of patients who have achieved pathologic complete response.	1 week after sugery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading.	7 months
3-year Local Recurrence Free Survival Rate	Defined as the proportion of patients who are not local recurrence or death at 3 years after enrollment.	3 years
3-year Progress Free Survival Rate	Defined as the proportion of patients who are not progress or death at 3 years after enrollment.	3 years
3-year Overall Survival Rate	Defined as the proportion of patients who are alive at 3 years after enrollment.	3 years
clinical complete response	Defined as the proportion of patients who have achieved clinical complete response.	up to 30 weeks
Major Pathologic Response	Defined as the proportion of patients who have achieved major pathologic response	1 week after sugery
Objective Response Rate	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.	through study completion，an average of 3 year
Anal Sphincter Retention Rate	Defined as the proportion of patients who retain anal sphincter	1 week after sugery
R0 resection rate	Defined as the proportion of patients who have achieved R0 resection.	1 week after sugery

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Fengpeng Wu, Professor, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: January 7, 2024
• First Submitted That Met QC Criteria: January 7, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: UGT1A1; liposomal irinotecan; total neoadjuvant therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Capecitabine; Irinotecan
• Other Study ID Numbers: CSPC-DEY-CRC-K08

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