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UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer

Primary Purpose

Rectal Cancer Stage III

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Neoadjuvant chemoradiotherapy based on irinotecan
Sponsored by
Zhejiang Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Cancer Stage III focused on measuring locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, irinotecan

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Pathologically confirmed rectal adenocarcinoma
  2. Clinical stage T3-4 and / or Nude positive, and the treatment plan is nCRT.
  3. Without distance metastases
  4. A need for tumor withdrawal.
  5. Aged 18-75 years old, regardless of gender.
  6. ECOG score 0-2.
  7. Detection of UGT1A1*6 and * 28 gene status.
  8. Be able to comply with the plan during the study period.
  9. Sign the inform consent

Exclusion Criteria:

  1. Pregnant or breastfeeding women
  2. Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ
  3. If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance.
  4. Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months
  5. Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases
  6. Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total bilirubin <1.5 times the normal upper limit; serum creatinine <1 times the normal upper limit; serum albumin ≥ 30g / L
  7. Anyone who is allergic to any research medication
  8. DPD deficiency

Sites / Locations

  • Zhejiang Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant chemoradiotherapy based on irinotecan

Arm Description

Locally advanced rectal cancer patients who were treated with irinotecan-based neoadjuvant chemoradiotherapy regimen can be enrolled in this group.

Outcomes

Primary Outcome Measures

Complete remission rate
The tumor disappeared completely and the tumor markers remained normal for at least 4 weeks.
Locally recurrence rate
The proportion of recurrent rectal tumors in the total population after the complete regression of rectal tumors
DFS
The time from complete regression of the tumor after neoadjuvant therapy or radical resection to the first recurrence or death
OS
The time from enrolled in the study to death caused by any cause
Toxicity effect
Any adverse reactions caused by neoadjuvant chemoradiotherapy or surgery

Secondary Outcome Measures

Full Information

First Posted
October 7, 2021
Last Updated
December 7, 2021
Sponsor
Zhejiang Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05148767
Brief Title
UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer
Official Title
Neoadjuvant Chemoradiation With Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer: A Real-Word Multi-center Study
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Anticipated)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
December 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To explore whether the application of irinotecan under the guidance of UGT1A1 gene in neoadjuvant chemotherapy and radiotherapy for locally advanced rectal cancer could improve the clinical efficacy in the real world.
Detailed Description
Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is the standard care of treatment for locally advanced rectal cancer (LARC), which could effectively reduce the risk of local recurrence, increase the chance of sphincter preservation, and effectively improve the quality of life of patients. However, only about 8% of patients can benefit from nCRT. Therefore, to improve the therapeutic effect of nCRT and retain the organ function of patients so as to improve their quality of life is the focus of the current investigation. In the previous study, the investigator have completed a series of clinical researches of irinotecan guided by UGT1A1 gene for nCRT in rectal cancer. A dose climbing study was firstly conducted to explore the maximum tolerable dose of irinotecan for nCRT in rectal cancer. The results indicated that the weekly dose intensity of irinotecan could be increased from 50mg/m2 to 80mg/m2 when the genotype of UGT1A1*28 locus was 6/6, and the weekly dose intensity of irinotecan could also reach 65mg/m2 when the genotype of irinotecan was 6/7 phenotype. Further analysis also demonstrated that there was a dose-effect relationship between the total dose of irinotecan and pathological complete remission (pCR). The recently published CinClare study is a 3-phase randomized controlled trial that doubles the pCR rate and the total CR rate in combination with irinotecan on the basis of capecitabine combined with radiotherapy. However, in the Aristotle study conducted in the United Kingdom at the same phase, it has not been proved that irinotecan could improve the pCR rate, and it is not known whether the difference between the two studies is completely attributed to the irinotecan dose. Therefore, the investigator designed this real-world study to explore whether irinotecan can indeed improve the treatment efficacy in the real world when using irinotecan under the guidance of UGT1A1 gene in nCRT for LARC. Any locally advanced rectal cancer patients treated with irinotecan-based neoadjuvant radiotherapy and chemotherapy can be enrolled in this study. It is expected that the results of this study could provide more basis for individualized treatment of LARC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer Stage III
Keywords
locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, irinotecan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
606 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant chemoradiotherapy based on irinotecan
Arm Type
Experimental
Arm Description
Locally advanced rectal cancer patients who were treated with irinotecan-based neoadjuvant chemoradiotherapy regimen can be enrolled in this group.
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant chemoradiotherapy based on irinotecan
Intervention Description
Patients with locally advanced rectal cancer treated with irinotecan-based chemoradiotherapy were enrolled in this study. The dose of irinotecan is determined by the genotype of UGT1A1.Concurrent Chemoradiotherapy: Radiation: 50Gy/25Fx; Capecitabine: 625mg/m2 bid Monday-Friday per week; Irinotecan: 80mg/m2 (UGT1A1*28 and *6: 6/6+GG) or 65mg/m2 (UGT1A1*28 and *6 :6/7+GG or 6/6+GA) or 50mg/m2 (UGT1A1*28 and *6 :7/7+GG or 6/6+AA or 6/7+GA).
Primary Outcome Measure Information:
Title
Complete remission rate
Description
The tumor disappeared completely and the tumor markers remained normal for at least 4 weeks.
Time Frame
3 months after neoadjuvant chemoradiotherapy
Title
Locally recurrence rate
Description
The proportion of recurrent rectal tumors in the total population after the complete regression of rectal tumors
Time Frame
Within 5 years after the end of treatment
Title
DFS
Description
The time from complete regression of the tumor after neoadjuvant therapy or radical resection to the first recurrence or death
Time Frame
Within 5 years after the end of treatment
Title
OS
Description
The time from enrolled in the study to death caused by any cause
Time Frame
Within 5 years after the end of treatment
Title
Toxicity effect
Description
Any adverse reactions caused by neoadjuvant chemoradiotherapy or surgery
Time Frame
Within 5 years after the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically confirmed rectal adenocarcinoma Clinical stage T3-4 and / or Nude positive, and the treatment plan is nCRT. Without distance metastases A need for tumor withdrawal. Aged 18-75 years old, regardless of gender. ECOG score 0-2. Detection of UGT1A1*6 and * 28 gene status. Be able to comply with the plan during the study period. Sign the inform consent Exclusion Criteria: Pregnant or breastfeeding women Those with other history of malignant disease in the past 5 years, except for cured skin cancer and cervical carcinoma in situ If there is an uncontrolled history of epilepsy, central nervous system disease or mental disorder, the investigator may determine that the clinical severity may hinder the signing of informed consent or affect the patient's oral medication compliance. Clinically severe (ie, active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or severe arrhythmia requiring medication intervention (see appendix 12), or a history of myocardial infarction in the last 12 months Organ transplantation requires immunosuppressive therapy Severe uncontrolled recurrent infections, or other serious uncontrolled concomitant diseases Subject blood routine and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g / L; absolute neutrophil count (ANC) ≥ 1.5 × 109 / L; Alanine transaminase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal; alkaline phosphatase (ALP) ≤2.5 times the normal upper limit; serum total bilirubin <1.5 times the normal upper limit; serum creatinine <1 times the normal upper limit; serum albumin ≥ 30g / L Anyone who is allergic to any research medication DPD deficiency
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ji Zhu, MD
Phone
571-88128142
Ext
+86
Email
leo.zhu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Quanquan Sun, MD
Phone
571-88128142
Ext
+86
Email
sunqq@zjcc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ji Zhu, MD
Organizational Affiliation
Zhejiang Cancer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ji Zhu, MD
Phone
571-88128142
Ext
+86
Email
leo.zhu@126.com
First Name & Middle Initial & Last Name & Degree
Quanquan Sun, MD
Phone
571-88128212
Ext
+86
Email
sunqq@zjcc.org.cn

12. IPD Sharing Statement

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UGT1A1-Based Irinotecan Therapy for Locally Advanced Rectal Cancer

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