Efficacy and Safety Comparison of Short-course Radiotherapy Followed by CapeOX Chemotherapy Plus Toripalimab With or Without Concurrent Surufatinib in Neoadjuvant Therapy for Mid-to-low Localized Rectal Cancer of High-risk Criteria

Summary

Why is this study conducted? The purpose of this study is to improve the treatment efficacy, particularly the pathological complete response rate, in patients with high-risk/extremely high-risk locally advanced rectal cancer (LARC). In recent years, with the combination of neoadjuvant chemoradiotherapy and immunotherapy, some progress has been made in the treatment of rectal cancer, but there are still problems of regional recurrence and distant metastasis. Therefore, developing new treatment strategies for these patients is particularly important.

The treatment of rectal cancer usually involves surgery, radiation therapy, and chemotherapy. The current treatment methods have gradually shifted towards neoadjuvant chemoradiotherapy combined with immunotherapy, and have shown good potential in some clinical trials. These studies suggest that combining short-range radiotherapy, anti angiogenic drugs, and immune checkpoint inhibitors may play an important role in improving patient prognosis and enhancing tumor response rates. However, the efficacy and safety of these plans in high-risk patients still need further validation.

In this context, the aim of our study is to compare the efficacy and safety of neoadjuvant short-course radiotherapy followed by four cycles of CapeOX chemotherapy combined with toripalimab, with or without concurrent surufatinib, in patients with mid-to-low locally advanced rectal cancer with high-risk factors identified by MRI (including any one or more of the following: cT4, cN2, EMVI+, MRF/CRM+, or lateral lymph node metastas. This study aims to promote treatment optimization for LARC patients and provide new ideas for future treatments.

Why are you invited to participate in this study? We would like to invite you to participate in this study as you have been diagnosed with high-risk or extremely high-risk locally advanced rectal cancer, which meets the inclusion criteria of this study. Specifically, you need to meet the conditions for pathological diagnosis, have a suitable tumor location, and not have serious comorbidities or other excluded diseases (such as recurrent rectal cancer, cardiac dysfunction, etc.). The final selection will be determined by the research doctor based on your actual situation.

What do you need to do to participate in this study? Participating in this study will require you to follow a series of steps. You need to undergo regular medical examinations and evaluations, including blood tests, imaging examinations, and anorectal function assessments. During the research period, you may also need to fill out a questionnaire and provide some biological samples (such as blood samples), which will be used for the analysis of drug efficacy. The frequency and specific content of each follow-up will be informed by the research team to ensure your participation throughout the entire treatment process. I hope you can cooperate with these research steps to help us better understand the effectiveness of this treatment plan.

What are the risks of participating in this study?

This study involves the use of neoadjuvant short course radiotherapy, PD-1 monoclonal antibody (Terizumab), and anti angiogenic therapy (Sofantinib). Participants may face the following risks:

Risk of neoadjuvant short course radiotherapy: Participants may experience severe side effects (≥ grade 3), including but not limited to severe diarrhea, third degree neutropenia, and third degree radiation dermatitis. These side effects may seriously affect the quality of life of patients.

Risk of PD-1 monoclonal antibody: Terriptylimab may cause immune related adverse reactions (irAEs), which can involve any organ. The commonly known irAEs include skin toxicity (such as papules and itching, with an incidence of 30% to 40%), diarrhea and/or colitis (8% to 19%), fatigue (16% to 24%), immune related hepatitis (5%), hypothyroidism (4% to 10%), and hyperthyroidism (4%). Overall, nearly two-thirds (about 2/3) of patients receiving immune checkpoint inhibitor therapy will experience varying degrees of irAEs, and the incidence of serious adverse events cannot be ignored.

Risk of anti angiogenic therapy: The use of sorafenib may lead to adverse reactions related to its anti angiogenic and immunomodulatory effects. Known common adverse reactions include proteinuria, hypertension, bleeding, liver dysfunction, diarrhea, etc., with an incidence rate of over 20%. Among serious adverse events (≥ grade 3), hypertension (29.7%), proteinuria (14.5%), liver dysfunction (12.8%), and bleeding (4.5%) are the most common. In rare cases, treatment-related deaths may occur due to gastrointestinal bleeding, cerebral hemorrhage, etc.

Handling of research related injuries? This study is an intervention study that does not add any additional risks beyond routine clinical diagnosis and treatment. If you suffer harm due to participating in the study, compensation or liability will be determined in accordance with relevant laws and regulations.

Conditions

• Rectal Cancer

Interventions

DRUG

Experimental Group

Patients in the experimental group of this study began continuous oral administration of sofentanil at a dose of 200 mg once daily, starting 2 days after completion of neoadjuvant short-course radiotherapy. The final dose was administered on day 14 of the last capecitabine cycle of the CapeOX chemotherapy regimen, resulting in a total oral administration period of 12 weeks. Both the experimental group and control group in this study will commence 4 cycles of CapeOX chemotherapy combined with toripalimab immunotherapy one week after completion of neoadjuvant short-course radiotherapy. \[CapeOX\] regimen: Oxaliplatin 130 mg/m², d1, IV (2-hour infusion); Capecitabine 1250 mg/m², p.o., d1-14, BID, Q3W; Toripalimab 240 mg, IV, d1, Q3W.

DRUG

Control group

One week after the completion of neoadjuvant short-course radiotherapy, patients will receive 4 cycles of CapeOX chemotherapy combined with toripalimab immunotherapy.CapeOX regimen:Oxaliplatin 130 mg/m², intravenous infusion for 2 hours on day 1;Capecitabine 1250 mg/m², orally, twice daily on days 1-14, every 3 weeks;Toripalimab 240 mg, intravenous infusion on day 1, every 3 weeks.

Sponsors & Collaborators

• The First Hospital of Jilin University

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-23

Primary Completion

2029-12-31

Completion

2029-12-31

Countries

• China

Study Locations