Involve-site Radiotherapy Combined With Chemotherapy and Immunotherapy as Neoadjuvant Treatment for Locally Advanced Rectal Cancer

NCT07161115 | Not Yet Recruiting Phase 2

• 1 other identifier: 1stChongqingMU-LLi
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery is the primary treatment for rectal cancer. However, in patients with locally advanced disease, direct surgery often fails to achieve complete tumor resection. In such cases, neoadjuvant therapy is required to downstage the tumor before surgery. The current standard neoadjuvant approach consists of preoperative radiotherapy and then surgery. Although effective, standard radiotherapy uses large target volumes, which results in significant toxicities, increased surgical complications, and reduced patient compliance and quality of life. In addition, excessive radiation fields can compromise the intensity and timing of systemic therapy, potentially increasing the risk of distant metastasis. This may be one of the key reasons why current neoadjuvant radiotherapy mainly improves local control but has not translated into prolonged overall survival. Emerging evidence suggests that combining immunotherapy with radiotherapy may further enhance treatment efficacy. However, large radiation fields may impair the effectiveness of immunotherapy. Therefore, reducing the radiotherapy target volume may not only decrease treatment-related toxicity but also augment the immunotherapy response. This clinical study is designed to evaluate whether reducing the radiotherapy target volume, when combined with chemotherapy and immunotherapy prior to surgery, can decrease radiotherapy-related toxicities and reduce the risk of distant metastasis, without increasing the local recurrence rate, compared with the current standard radiotherapy fields. The ultimate goal is to improve the efficacy of neoadjuvant therapy in locally advanced rectal cancer while minimizing treatment toxicity, thereby providing new strategies and evidence for preoperative management.

Conditions

Rectal Adenocarcinoma

Keywords

rectal cancers; radiotherapy; immunotherapy; Reducing the radiation field for radiotherapy

Outcome Measures

Primary Outcomes (1)

• Two-year local control rate after rectal cancer surgery

  Incidence of pelvic recurrence or distant metastasis within 2 years after surgery among the enrolled cohort

  At two years post-surgery

Secondary Outcomes (7)

• Pathological Complete Response (pCR) Rate

  At the time of surgery

• Resection Rate

  At the time of surgery

• Incidence of Grade ≥3 Radiation-induced Proctitis

  From the start of radiotherapy until 2 years after surgery

• Overall Survival (OS)

  Up to 5 years after surgery

• Objective Response Rate (ORR)

  From baseline until surgery

Study Arms (3)

Involve-site Short-Course Radiotherapy

EXPERIMENTAL

Radiation: Reduced-field short-course radiotherapy; Drug: Immunotherapy combined with chemotherapy

Standard long-course radiotherapy

ACTIVE COMPARATOR

Radiation: Standard long-course radiotherapy; Drug: Chemotherapy

Standard short-course radiotherapy

ACTIVE COMPARATOR

Drug: Immunotherapy combined with chemotherapy; Radiation: Standard short-course radiotherapy

Interventions

Reduced-field short-course radiotherapy RADIATION

A dose of 25 Gy in 5 fractions was delivered as short-course radiotherapy, with one fraction per day, completing treatment within one week. The target volume was delineated using both CT and MRI. Compared to conventional radiotherapy fields, the irradiated volume was significantly reduced to include only the primary tumor and any metastatic lymph nodes as identified on MRI and CT.

Involve-site Short-Course Radiotherapy

Immunotherapy combined with chemotherapy DRUG

After completion of radiotherapy, chemotherapy with the XELOX regimen (oxaliplatin 130 mg/m² on day 1 plus capecitabine 1500 mg/m² on days 1-14, every 3 weeks) was initiated in combination with sintilimab immunotherapy (200 mg every 3 weeks) for 4 cycles.

Involve-site Short-Course Radiotherapy; Standard short-course radiotherapy

Standard short-course radiotherapy RADIATION

"Patients in the standard short-course radiotherapy group will receive 25 Gy in 5 fractions, once daily. Target volumes will be delineated according to the 2023 Guidelines for Target Volume Delineation and Planning of Rectal Cancer (National Cancer Center/National Cancer Quality Control Center), including the primary tumor, mesorectal region, and internal iliac and obturator lymph node drainage areas."

Standard short-course radiotherapy

Standard long-course radiotherapy RADIATION

Patients in the standard long-course radiotherapy group will receive 50 Gy in 25 fractions, once daily, five days per week, with concurrent oral capecitabine chemotherapy. Target volumes will be delineated according to the 2023 Guidelines for Target Volume Delineation and Planning of Rectal Cancer (National Cancer Center/National Cancer Quality Control Center), including the primary tumor, mesorectal region, and internal iliac and obturator lymph node drainage areas.

Standard long-course radiotherapy

Chemotherapy DRUG

Two weeks after the completion of radiotherapy, patients will receive four cycles of CAPOX chemotherapy.

Standard long-course radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agrees to participate and provides written informed consent
• Age 18 to 75 years, male or female
• Histologically confirmed rectal adenocarcinoma
• MRI confirms that the upper margin of the tumor is ≤12 cm from the anal verge
• ECOG performance status of 0-1
• Clinical stage T3-T4 or N+ and circumferential resection margin (CRM) positive by imaging evaluation; lateral lymph nodes negative
• Immunohistochemistry or genetic testing indicates pMMR or MSS status
• Adequate organ function and bone marrow reserve

You may not qualify if:

• Presence of distant metastasis
• Prior pelvic radiotherapy
• Chemotherapy or immunotherapy within the past 3 months
• Refusal to undergo radical surgery for rectal cancer
• Concurrent active malignancy other than rectal cancer
• Positive antinuclear antibody (ANA)
• History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, autoimmune hepatitis)
• Elevated troponin above the normal range
• Active tuberculosis
• Positive hepatitis B surface antigen (HBsAg) or detectable HBV DNA
• Positive for hepatitis C virus (HCV), syphilis, or HIV
• Severe comorbid conditions (e.g., serious infection, severe bone marrow suppression, psychiatric disorder) deemed unsuitable for participation by the investigator
• Pregnant or breastfeeding women
• Any other contraindications to radiotherapy, chemotherapy, or immunotherapy

Sponsors & Collaborators

• Longhao Li: lead

Study Sites (1)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Longhao Li, M.D.

  First Affiliated Hospital of Chongqing Medical University

  STUDY CHAIR

Central Study Contacts

Longhao Li, M.D.

CONTACT

+86-02389011516; llh@hospital.cqmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: August 29, 2025
• First Posted: September 8, 2025
• Study Start: September 19, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2030
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data available 6 months after primary results publication, for 5 years.
• Access Criteria: Available to researchers with a scientifically sound proposal. Requests reviewed by the study steering committee; a data use agreement must be signed.

Locations

CN (1)