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

NCT06017583 | Recruiting Phase 3

• 1 other identifier: 2023-S845-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Neoplasms

Keywords

Rectal cancer; Tislelizumab; SIB IMRT

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks~18 weeks

Secondary Outcomes (3)

• Side effects

  6monthes, 3years

• Overall survival

  3 years

• Disease free survival

  3 years

Study Arms (2)

Experimental arm

EXPERIMENTAL

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).

Drug: Tislelizumab; Drug: Capecitabine; Drug: Oxaliplatin; Radiation: SIB-IMRT

Control arm

PLACEBO COMPARATOR

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

Drug: Capecitabine; Drug: Oxaliplatin; Radiation: IMRT

Interventions

Tislelizumab DRUG

Tirellizumab was administered intravenously at 200mg/d1, 21 days per cycle, with at least 4 cycles completed.

Experimental arm

Capecitabine DRUG

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.

Control arm; Experimental arm

Oxaliplatin DRUG

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.

Control arm; Experimental arm

SIB-IMRT RADIATION

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.

Experimental arm

IMRT RADIATION

The whole dose of the clinical target volume is 5000 cGy with intensity-modulated radiotherapy.

Control arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yong Zhang,MD: lead

Study Sites (1)

First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

tislelizumab; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: First Affiliated Hospital of Guangxi Medical University

Model Details: The random number table method.

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: August 30, 2023
• Study Start: September 1, 2023
• Primary Completion: August 31, 2024
• Study Completion (Estimated): August 31, 2026
• Last Updated: October 11, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)