Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

Rectal Cancer Clinical Trial

Official title:

Multicenter Prospective Randomized Clinical Trial of Neoadjuvant Chemoradiation Therapy Combined With Immunotherapy for MSS Ultra-low Rectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05215379
• Other study ID #: CHCRS-Immunity
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: July 2023
• Source: Changhai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

At present, there are no relevant studies or reports on the effect of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer. Studied in this paper combin neoadjuvant chemoradiation with immune therapy, carry out "Multicenter prospective randomized clinical trial of neoadjuvant chemoradiation therapy combined with immunotherapy for MSS ultra-low rectal cancer" in order to provide a high-level evidence-based medical evidence for ultra-low rectal cancer treatment and improve ultra-low rectal cancer diagnosis and treatment effect.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: April 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Ultra low rectal cancer patients evaluated by multidisciplinary team to perform APR

• Patients who have a strong desire to preserve the anus and are willing to accept neoadjuvant treatment
• 18 years old = age = 75 years old, no gender limit;
• Colonoscopy, intracavitary ultrasound and pelvic high-resolution MRI (or enhanced CT) were diagnosed as extremely low rectal cancer within 5 cm from the lower edge of the tumor to the anal edge. The baseline clinical stage is T1-3aN0-1M0, and the size of the tumor <1/2 circle;
• Histopathological diagnosis of rectal adenocarcinoma; tumor biopsy immunohistochemistry showed pMMR, that is, MSH1, MSH2, MSH6 and PMS2 four proteins are positive, or genetic testing suggests MSI-L or MSS.
• The patient has good compliance and can come to the hospital for reexamination as required;
• ECOG physical status score 0-1 points;
• Have not received anti-tumor and immunotherapy before being selected;
• 8. Laboratory inspections must meet the following standards: i. White blood cell count =3.5×109/L, absolute neutrophil count =1.8×109/L, platelet count =100×10^9/L, hemoglobin =100g/L; ii. INR=1.5, and APTT=1.5 times the upper limit of normal value or partial prothrombin time (PTT)=1.5 times the upper limit of normal value; iii. Total bilirubin=1.25 times the upper limit of normal; ALT and AST=5 times the upper limit of normal; iv. 24h creatinine clearance rate =50mL/min or blood creatinine =1.5 times the upper limit of normal.
• Voluntarily sign the informed consent form;

Exclusion Criteria:

• History of other malignant diseases in the past 5 years;
• Patients with metastases ;
• Patients with intestinal obstruction, intestinal perforation, intestinal bleeding, etc. who need emergency surgery;
• Those who are known to be allergic to capecitabine, oxaliplatin, PD-1 monoclonal antibody and other drugs;
• Patients with poorly differentiated adenocarcinoma, signet ring cell carcinoma, and mucinous adenocarcinoma;
• The patient is accompanied by any unstable systemic diseases, including but not limited to: severe infection, uncontrolled diabetes, hypertension that cannot be controlled by drugs, unstable angina, cerebrovascular accident or transient cerebral ischemia, myocardium Infarction, congestive heart failure, severe arrhythmia requiring medication, liver, kidney or metabolic diseases; diseases that affect the life of the patient.
• The patient's accompanying diseases (such as mental illness, etc.) or conditions (such as alcohol or drug abuse, etc.) will increase the patient's risk of receiving experimental drug treatment or affect the patient's compliance with the trial requirements, or may confuse the research results;
• Within 30 days before screening, the patient has received any other experimental drug treatment or participated in another interventional clinical trial;
• Women who are pregnant or breastfeeding or who intend to become pregnant or breastfeeding during the study period; men or women who are unwilling to take effective contraceptive measures;
• The investigator judges that the patient is not suitable to participate in other situations such as the clinical trial.

Related Conditions & MeSH terms

• Immunotherapy
• Microsatellite Instability
• Rectal Cancer
• Rectal Neoplasms

Intervention

Drug:
• xintilimab injection
neoadjuvant chemoradiation therapy +xintilimab injection 200mg/3week 4cycle

Other:
• Control
neoadjuvant chemoradiation therapy

Locations

Country	Name	City	State
China	Department of Colorectal Surgery in Changhai Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Changhai Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of cCR	Rate of patients who achieve clinical complete response	2 years
Secondary	The rate of organ preservation	Rate of patients who achieve organ preservation	2 years
Secondary	The rate of anus preservation	Rate of patients who achieve anus preservation	2 years
Secondary	pCR rate	Rate of pCR patients after surgery	2 years
Secondary	Disease free survival(DFS)	DFS was defined as the duration from the date of randomization to the date of the first recurrence (local, distant, or mixed) or death.	2 years
Secondary	overall survival(OS)	OS was calculated from the date of randomization.	2 years
Secondary	quality of life	The QoL was assessed by EORTC QOL Core Questionnaire.	2 years