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Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer

Primary Purpose

Rectal Neoplasms

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Tislelizumab
Capecitabine
Oxaliplatin
SIB-IMRT
IMRT
Sponsored by
Yong Zhang,MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rectal Neoplasms focused on measuring Rectal cancer, Tislelizumab, SIB IMRT

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Aged 18 to 70 years. The pathological type of rectal cancer diagnosed by histopathology is adenocarcinoma. Patients with T3-4 in the eighth AJCC stage or positive regional lymph node and no distant metastasis. Having at least one measurable lesion according to RECIST 1.1. ECOG score 0-1. Expected survival time ≥6 months. Major organ function is normal, that is, meeting the following criteria: blood routine: HB≥90g/L, ANC≥1.5×109/L, PLT≥80×109/L; Biochemical examination of ALB≥30g/L, TBIL≤1.5 ULN, ALT and AST≤2.5 ULN, plasma Cr≤1.5 ULN or creatinine clearance ≥60 ml/min. Subjects volunteered to join the study, signed the informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Patients have had or currently have other malignant tumors within 5 years. Patients allergic or sensitive to any drug in the study protocol. Patients innate or acquired immune deficiency (e.g. HIV infection). The presence of any active, known or suspected autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, hypothyroidism, etc.); The subject had vitiligo. Subjects with asthma require bronchodilators for medical intervention. The presence of active infections requiring systemic treatment. The subject has previously received other PD-1 or PD-L1, or CTLA-4 antibody therapy, or other drug therapy targeting immunoregulatory receptor preparations. Unrelieved toxic effects above CTCAE grade 1 due to any previous treatment, excluding alopecia. Patients with a history of myocardial infarction or stroke, unstable angina pectoris, decompensated heart failure or deep vein thrombosis. Patients with long-term untreated wounds or fractures, major surgical operations or severe traumatic injuries, fractures or ulcers within 4 weeks. Pregnant or lactating women. Patients with liver and kidney dysfunction. Patients with a history of abuse of psychotropic drugs and unable to abstain or patients with mental disorders. Patients who have participated in clinical trials of other drugs within 4 weeks. Patients with concomitant diseases that, in the judgment of the investigator, seriously endanger the patient's safety or affect the patient's completion of the study. The investigator judged that participation in this study was not conducive to the maximum benefit of the subjects.

Sites / Locations

  • First Affiliated Hospital of Guangxi Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental arm

Control arm

Arm Description

The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).

The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.

Outcomes

Primary Outcome Measures

Complete response rate
Include in pathological complete response rate and clinical complete response rate. MRI/CT will be used for evaluating the carcinoma status. Pathological complete response rate will be evaluated by surgery.

Secondary Outcome Measures

Side effects
Myelosuppression, radiation enteritis, radiothermitis
Overall survival
OS was calculated from the date of entry into the study to the date of death or the last follow-up visit.
Disease free survival
DFS was calculated from the date of entry into the study to the date of the time from the beginning of randomization to the disease recurrence or progression or death from any cause.

Full Information

First Posted
August 18, 2023
Last Updated
October 10, 2023
Sponsor
Yong Zhang,MD
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1. Study Identification

Unique Protocol Identification Number
NCT06017583
Brief Title
Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer
Official Title
Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With Simultaneous Integrated Boost Intensity-modulated Radiotherapy in the Treatment of Locally Advanced Rectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2023 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yong Zhang,MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study aims to evaluate the efficacy and safety of tislelizumab combined with simultaneous integrated boost intensity-modulated radiotherapy in treating locally advanced rectal cancer. To explore a new PD-1 inhibitor adjuvant chemotherapy model combined with radiotherapy to treat locally advanced rectal cancer.
Detailed Description
This is a randomized controlled trial (RCT). Patients with T3-4 in the 8th AJCC stage or positive regional lymph nodes and no distant metastases will be enrolled. Forty-eight patients will be enrolled by inclusion and exclusion criteria. The enrolled patients will be randomly divided into experimental and control groups (twenty-four patients for each group) to receive preoperative neoadjuvant therapy. The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving complete tislelizumab treatment for at least 4 cycles (21 days per cycle). The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group. The tumor size will be measured in MRI or CT images, and side effects will be recorded. The primary outcome was CR rate (pathological complete response rate and clinical complete response rate), and secondary outcomes were side effects and 3-year OS and DFS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasms
Keywords
Rectal cancer, Tislelizumab, SIB IMRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The random number table method.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental arm
Arm Type
Experimental
Arm Description
The experimental group will receive concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and concurrent capecitabine chemotherapy, and complete 2 ~ 4 cycles of XELOX chemotherapy, while receiving full tislelizumab treatment for at least 4 cycles (21 days per cycle).
Arm Title
Control arm
Arm Type
Placebo Comparator
Arm Description
The control group received intensity-modulated radiotherapy (IMRT) without tirellizumab, and the other treatment regiments were consistent with the experimental group.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
Tirellizumab was administered intravenously at 200mg/d1, 21 days per cycle, with at least 4 cycles completed.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Oral capecitabine 825mg/m2 bid, radiotherapy day concurrent chemotherapy. Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Chemotherapy regimen after radiotherapy: XELOX regimen: oxaliplatin intravenous infusion of 130mg/m2/d1+ oral capecitabine 1000mg/m2 bid/ d1-14, 21 days per cycle, at least 2 cycles completed.
Intervention Type
Radiation
Intervention Name(s)
SIB-IMRT
Intervention Description
The tumor and the related mesenteric region 1cm above and below were simultaneously integrated boost to 5600cGy with the intensity-modulated radiotherapy. The other dose for clinical target volume is 5000 cGy.
Intervention Type
Radiation
Intervention Name(s)
IMRT
Intervention Description
The whole dose of the clinical target volume is 5000 cGy with intensity-modulated radiotherapy.
Primary Outcome Measure Information:
Title
Complete response rate
Description
Include in pathological complete response rate and clinical complete response rate. MRI/CT will be used for evaluating the carcinoma status. Pathological complete response rate will be evaluated by surgery.
Time Frame
12 weeks~18 weeks
Secondary Outcome Measure Information:
Title
Side effects
Description
Myelosuppression, radiation enteritis, radiothermitis
Time Frame
6monthes, 3years
Title
Overall survival
Description
OS was calculated from the date of entry into the study to the date of death or the last follow-up visit.
Time Frame
3 years
Title
Disease free survival
Description
DFS was calculated from the date of entry into the study to the date of the time from the beginning of randomization to the disease recurrence or progression or death from any cause.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 to 70 years. The pathological type of rectal cancer diagnosed by histopathology is adenocarcinoma. Patients with T3-4 in the eighth AJCC stage or positive regional lymph node and no distant metastasis. Having at least one measurable lesion according to RECIST 1.1. ECOG score 0-1. Expected survival time ≥6 months. Major organ function is normal, that is, meeting the following criteria: blood routine: HB≥90g/L, ANC≥1.5×109/L, PLT≥80×109/L; Biochemical examination of ALB≥30g/L, TBIL≤1.5 ULN, ALT and AST≤2.5 ULN, plasma Cr≤1.5 ULN or creatinine clearance ≥60 ml/min. Subjects volunteered to join the study, signed the informed consent, had good compliance, and cooperated with follow-up. Exclusion Criteria: Patients have had or currently have other malignant tumors within 5 years. Patients allergic or sensitive to any drug in the study protocol. Patients innate or acquired immune deficiency (e.g. HIV infection). The presence of any active, known or suspected autoimmune disease (such as, but not limited to, interstitial pneumonia, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, hypothyroidism, etc.); The subject had vitiligo. Subjects with asthma require bronchodilators for medical intervention. The presence of active infections requiring systemic treatment. The subject has previously received other PD-1 or PD-L1, or CTLA-4 antibody therapy, or other drug therapy targeting immunoregulatory receptor preparations. Unrelieved toxic effects above CTCAE grade 1 due to any previous treatment, excluding alopecia. Patients with a history of myocardial infarction or stroke, unstable angina pectoris, decompensated heart failure or deep vein thrombosis. Patients with long-term untreated wounds or fractures, major surgical operations or severe traumatic injuries, fractures or ulcers within 4 weeks. Pregnant or lactating women. Patients with liver and kidney dysfunction. Patients with a history of abuse of psychotropic drugs and unable to abstain or patients with mental disorders. Patients who have participated in clinical trials of other drugs within 4 weeks. Patients with concomitant diseases that, in the judgment of the investigator, seriously endanger the patient's safety or affect the patient's completion of the study. The investigator judged that participation in this study was not conducive to the maximum benefit of the subjects.
Facility Information:
Facility Name
First Affiliated Hospital of Guangxi Medical University
City
Nanning
State/Province
Guangxi
ZIP/Postal Code
530021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Zhang, PhD
Phone
13607884001
Email
zhangyonggx@163.com
First Name & Middle Initial & Last Name & Degree
Shanshan Ma, PhD
Phone
13557994302
Email
mashanshan@gxmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Neoadjuvant Chemotherapy With PD-1 Inhibitors Combined With SIB-IMRT in the Treatment of Locally Advanced Rectal Cancer

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