The Effects of Neoadjuvant Tislelizumab Combined With Chemotherapy in Locally Advanced MSS Rectal Cancer

NCT06254521 | Recruiting Phase 2 DMC

• 1 other identifier: HOYT
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced MSS rectal cancer.

Conditions

Rectal Cancer; Rectal Cancer Stage II; Rectal Cancer Stage III

Keywords

locally advanced rectal cancer; neoadjuvant; PD-1

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors

  7days of postoperative pathological examination

Secondary Outcomes (9)

• Complete Clinical Response(cCR) rate

  5 days before surgery

• 3-year disease-free survival(DFS) rate

  36 months from date of the patient signs the informed consent form

• 3-year overall survival(OS) rate

  36 months from date of the patient signs the informed consent form

• the rate of adverse events(AEs)

  From the first day of immunotherapy until 6 months after the end of treatment

• the rate of immune-related adverse events(irAEs)

  From the first day of immunotherapy until 6 months after the end of treatment

Other Outcomes (2)

• T lymphocyte

  1-7 days before treatment, 1-7 days before surgery, 1 day after surgery, 3 months after surgery, and 6 months after surgery

• Molecular pathological analysis of tumor tissue

  Tumor tissue was obtained 1 month before treatment and analyzed 36 months after treatment

Study Arms (1)

neoadjuvant Tislelizumab combined with chemotherapy

EXPERIMENTAL

Patients with locally advanced rectal cancer who met the inclusion criteria received two or four cycles of Tislelizumab combined Capecitabine and Oxaliplatin regimen chemotherapy and were evaluated by enhanced CT and MRI\\TRUS. Then, these patients will receive curative surgery for rectal cancer. Interventions: Drug: Oxaliplatin Drug: Capecitabine Drug: Tislelizumab Procedure: curative surgery for rectal cancer

Drug: Tislelizumab combined with chemotherapy

Interventions

Tislelizumab combined with chemotherapy DRUG

Drug: Oxaliplatin Oxaliplatin 130mg/m2 for chemotherapy on Day 1 every 3 weeks and repeat for 2 or 4 cycles. The dose reduction protocol for oxaliplatin-induced toxicity was implemented according to the report in BJC (2018) 118:1322-1328. Drug: Capecitabine Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy from Day 1 to Day 14 every 3 weeks and repeat for 2 or 4 cycles. The dose reduction protocol for capecitabine-induced toxicity was implemented according to the report in BJC (2018) 118:1322-1328. Drug: Anti-PD-1 Monoclonal Antibody 200 mg on Day 1 every 3 weeks and repeat for 2 or 4 cycles. The incidence of adverse events with Anti-PD-1 Monoclonal Antibodies is relatively low. The PD-1 monoclonal antibody (Tislelizumab) dose adjustment was implemented according to the prescribing information. Other Names: Tislelizumab Procedure: Colectomy The specific surgical approach, whether it be laparoscopic

neoadjuvant Tislelizumab combined with chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years old and ≤70 years old.
• Pathologically diagnosed MSS ((confirmed by microsatellite stable detection or next-generation target sequencing) or (confirmed by immunohistochemistry)) colon adenocarcinoma.
• The lower edge of the tumor is less than 12cm from the anus as measured by colonoscopy and MRI,or TRUS.
• It was confirmed by magnetic resonance imaging (MRI) or intracavitary ultrasound of the rectum as T3-4 or N+, and M0 by enhanced CT.
• The ECOG physical status score is 0-1.
• Life expectancy is expected to be more than 1 year.
• First diagnosis, no previous anti-tumor treatment received, and no chemotherapy contraindications.
• Appropriate organ function is defined as follows: Hemoglobin level ≥ 90g/L, Neutrophil count ≥ 1.5×10\^9/L, Platelet count ≥ 75×10\^9/L, Serum total bilirubin ≤ 1.5× the upper limit of normal (UNL), Aspartate aminotransferase (AST) ≤ 2× UNL, Alanine aminotransferase (ALT) ≤ 3× UNL, Serum creatinine ≤ 1.5× UNL.
• Informed consent, able to understand the study protocol and willing to participate in the study, and will provide written informed consent.

You may not qualify if:

• Early rectal cancer (T1-2N0M0); The lower margin of the tumor was less than 5cm from the anus and T4. APR(combined abdominal perineal resection) is required;
• Multifocal colorectal cancer.
• Tumor obstruction or high risk of obstruction, bleeding, and/or perforation requiring emergency surgery or stent placement.
• Cannot tolerate chemotherapy or immunotherapy, such as but not limited to bone marrow suppression.
• History of malignant tumors, except for basal cell carcinoma, papillary thyroid carcinoma, and various in situ cancers.
• Acute exacerbation of important organ diseases (such as but not limited to COPD, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), ASA score \> 3 points.
• Mental disorders, illiteracy, or language communication barriers that prevent the understanding of the study protocol.
• Peripheral sensory neuropathy, unable to receive oxaliplatin-based chemotherapy.
• Continuous use of glucocorticoids for more than 3 days within 1 month prior to signing the informed consent form, or having comorbidities requiring the use of glucocorticoid therapy.
• Unable to undergo enhanced CT examination
• Pregnancy or lactation.
• Refused to participate in this study.
• Other situations in which the researcher deems unsuitable for this study.

Sponsors & Collaborators

• First Affiliated Hospital of Guangxi Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy

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)

Therapeutics

Study Officials

• Hui Li, Professor

  First Affiliated Hospital of Guangxi Medical University

  STUDY CHAIR

Central Study Contacts

Sen Zhang, Professor

CONTACT

13407738560; zs0771@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy chief physician

Model Details: Patients with locally advanced rectal cancer who met the inclusion criteria received two or four cycles of Tislelizumab combined Capecitabine and Oxaliplatin regimen chemotherapy and were evaluated by enhanced CT and MRI\\TRUS. Then, these patients will receive curative surgery for rectal cancer. Interventions: Drug: Oxaliplatin Drug: Capecitabine Drug: Tislelizumab Procedure: curative surgery for rectal cancer

Study Record Dates

• First Submitted: January 1, 2024
• First Posted: February 12, 2024
• Study Start: February 22, 2024
• Primary Completion: December 30, 2024
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: We will share the research proposal after registration; Primary study endpoint data were shared 15 days after surgery; All data will be shared 3 years after enrollment
• Access Criteria: Clinician or researcher

Locations

CN (1)