Rectal Cancer, Rectal Cancer Stage II, Rectal Cancer Stage III
Conditions
Keywords
locally advanced rectal cancer, neoadjuvant, PD-1
Brief summary
This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced MSS rectal cancer.
Detailed description
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME). Pelvic chemoradiotherapy for locally advanced rectal cancer reduces the risk of disease recurrence in the pelvis to less than 10% and has been standard care in North America since 1990.However, it is associated with short-term and long-term toxic effects that can adversely affect quality of life and physical function. Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death 1 (PD-1) monoclonal antibodies for neoadjuvant therapy. The study will conduct 2 or 4 cycles of Tislelizumab with Oxaliplatin and Capecitabine, followed by TME surgery. This study's primary endpoint is the proportion of pCR in the pathological specimens of surgically resected tumors.
Interventions
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
Sponsors
First Affiliated Hospital of Guangxi Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) rate | 7days of postoperative pathological examination | the proportion of tumor regression grades 0 (TRG0, disappearance of tumor cells) in the pathological specimens of surgically resected tumors |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Clinical Response(cCR) rate | 5 days before surgery | cCR:After non-surgical antitumor therapy, physical examination and auxiliary examination(CT and MRI ) found no local evidence of tumor residue. |
| 3-year disease-free survival(DFS) rate | 36 months from date of the patient signs the informed consent form | DFS:From date of the patient signs the informed consent form until the date of earliest occurrence of the patient's tumor recurrence or death, whichever came first.assessed up to 36 months.CT, MRI and colonoscopy were used to evaluate tumor recurrence. |
| 3-year overall survival(OS) rate | 36 months from date of the patient signs the informed consent form | OS:From the date of the patient signs the informed consent form until the date of the patient's death.assessed up to 36 months. |
| the rate of adverse events(AEs) | From the first day of immunotherapy until 6 months after the end of treatment | Adverse events (NCI CTC AE 5.0) that occurred from the first day of chemotherapy to one day of treatment end (up to half a year). |
| the rate of immune-related adverse events(irAEs) | From the first day of immunotherapy until 6 months after the end of treatment | Immune-related adverse events (NCCN irAEs (2021)) that occurred from the first day of immunotherapy to one day of treatment end (up to half a year). |
| Retain anal proportions | immediately after the surgery | The proportion of cases with anal retention in all patients undergoing surgery |
| 3-year local recurrence rate | 36 months from date of the patient signs the informed consent form | From the date of the patient signs the informed consent form until the date of the local recurrence, assessed up to 36 months. CT, MRI and colonoscopy were used to evaluate local recurrence. |
| the rate of R0 resection | 7 days of postoperative pathological examination | the rate of a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed |
| the rate of surgical complication during or after operation | From the day of surgery to 30 days after the operation | From the day of surgery to 30 days after the operation, including intraoperative and postoperative complications(bleeding，anastomotic fistula，intestinal obstruction，Anastomotic stenosis，Surgical site infection（SSI），urinary retention，sexual dysfunction) |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | Cells with cellular immune function. The types and counts of T cells are analyzed using flow cytometry |
| Molecular pathological analysis of tumor tissue | Tumor tissue was obtained 1 month before treatment and analyzed 36 months after treatment | Whole exome gene sequencing is performed on tumor specimens to analyze the gene status |
Countries
China
Contacts
Primary ContactSen Zhang, Professor
Outcome results
None listed