Combining chemoradiation and immunotherapy for ultra-low rectal cancer

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

This study is testing whether combining chemotherapy and radiation with immunotherapy can improve treatment outcomes for patients with ultra-low rectal cancer.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05215379 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of neoadjuvant chemoradiation therapy combined with immunotherapy specifically for patients with microsatellite stable (MSS) ultra-low rectal cancer. The study aims to provide high-level evidence for improving treatment outcomes in this patient population by evaluating the efficacy of the combination therapy. Participants will undergo a multicenter prospective randomized approach to assess the safety and effectiveness of the treatment regimen. The trial is designed to gather data that could enhance the diagnosis and treatment strategies for ultra-low rectal cancer.

Who should consider this trial

Good fit: Ideal candidates are patients aged 18 to 75 with ultra-low rectal cancer who are willing to undergo neoadjuvant treatment and have not previously received anti-tumor or immunotherapy.

Not a fit: Patients with advanced rectal cancer beyond the specified clinical stage or those who have previously undergone anti-tumor therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes and quality of life for patients with ultra-low rectal cancer.

How similar studies have performed: This approach is novel, as there are currently no relevant studies on the combination of neoadjuvant chemoradiation therapy and immunotherapy for MSS ultra-low rectal cancer.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai

• Department of Colorectal Surgery in Changhai Hospital — Shanghai, Shanghai, China (Recruiting)

Conditions Neoadjuvant Chemoradiation Therapy; Rectal Cancer; Immunotherapy; Microsatellite Instability Low