Clinical trial NCT06254521: The Effects of Neoadjuvant Tislelizumab Combined With Chemotherapy in Locally Advanced MSS Rectal Cancer
Official title: Neoadjuvant Treatment of Locally Advanced MSS Rectal Cancer With Tislelizumab Combined With CAPOX Regimen: a Prospective, Single-arm, Single-center, Exploratory Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Rectal Cancer Stage II
Rectal Cancer Stage III
Keywords: locally advanced rectal cancer
neoadjuvant
PD-1
Lead sponsor: First Affiliated Hospital of Guangxi Medical University
Sponsor class: OTHER
First posted: 2024-02-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 \&gt; 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.

Primary outcomes:
measure: Pathological complete response (pCR) rate
timeFrame: 7days of postoperative pathological examination
Secondary outcomes:
measure: Complete Clinical Response(cCR) rate
timeFrame: 5 days before surgery
measure: 3-year disease-free survival(DFS) rate
timeFrame: 36 months from date of the patient signs the informed consent form
measure: 3-year overall survival(OS) rate
timeFrame: 36 months from date of the patient signs the informed consent form
measure: the rate of adverse events(AEs)
timeFrame: From the first day of immunotherapy until 6 months after the end of treatment
measure: the rate of immune-related adverse events(irAEs)
timeFrame: From the first day of immunotherapy until 6 months after the end of treatment
measure: the rate of R0 resection
timeFrame: 7 days of postoperative pathological examination
measure: the rate of surgical complication during or after operation
timeFrame: From the day of surgery to 30 days after the operation
measure: Retain anal proportions
timeFrame: immediately after the surgery
measure: 3-year local recurrence rate
timeFrame: 36 months from date of the patient signs the informed consent form
Other outcomes:
measure: T lymphocyte
timeFrame: 1-7 days before treatment, 1-7 days before surgery, 1 day after surgery, 3 months after surgery, and 6 months after surgery
measure: Molecular pathological analysis of tumor tissue
timeFrame: Tumor tissue was obtained 1 month before treatment and analyzed 36 months after treatment
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: Hui Li, Professor
role: STUDY_CHAIR
References: