Node-Sparing Short-Course Radiation with CAPOX and Sintilimab for MSS Locally Advanced Colon Cancer: a Randomized, Prospective, Multicenter Study

NCT06594692 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: mRCAT-C
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to evaluate the use of node-sparing short-course radiotherapy combined with chemotherapy and Sintilimab, or chemotherapy alone, as neoadjuvant therapy for MSS-type locally advanced colon cancer. The goal is to explore the efficacy and safety of combining node-sparing short-course radiotherapy with chemotherapy and immunotherapy in the neoadjuvant setting for MSS-type locally advanced colon cancer, while also investigating the specific role of regional lymph nodes in tumor immunotherapy.

Conditions

Microsatellite Stable (MSS) Colon Cancer; Locally Advanced Colon Cancer

Keywords

Locally Advanced Colon Cancer; Microsatellite Stable (MSS) Colon Cancer; Node-Sparing Radiotherapy; Short-Course Radiotherapy; Sintilimab

Outcome Measures

Primary Outcomes (1)

• pathological complete response rate

  The tumor specimen from node-sparing neoadjuvant chemoradiotherapy combined with immunotherapy, followed by sequential CME (complete mesocolic excision) surgery, showed no presence of cancer cells or lymph node metastasis under microscopic examination (ypT0N0M0).

  2 weeks after surgery

Secondary Outcomes (10)

• R0 resection rate

  2 weeks after surgery

• Tumor downstaging rate

  2 weeks after surgery

• The 3-year Event-Free Survival

  3 years post-treatment

• Objective Response Rate

  2 weeks after surgery

• The 3-year Local Recurrence Rate

  3 years post-treatment

Study Arms (2)

Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab

EXPERIMENTAL

Intervention Procedure: 1. Radiotherapy: Short-course radiotherapy is administered, with a total dose of 25Gy (5Gy per session for 5 sessions) targeting the primary tumor. 2. Chemotherapy and Immunotherapy: On the 8th day after the start of radiotherapy, CAPOX chemotherapy combined with Sintilimab is initiated for 4 cycles. 3. Surgery: One week after the completion of chemotherapy and immunotherapy, patients will undergo radical total mesorectal excision surgery. 4. Postoperative Adjuvant Chemotherapy: Starting 3-4 weeks after surgery, patients will resume CAPOX chemotherapy for an additional 4 cycles as adjuvant treatment.

Drug: Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab

Preoperative CAPOX Regimen as Neoadjuvant Therapy

ACTIVE COMPARATOR

Intervention Procedure: 1. Chemotherapy: Administer CAPOX chemotherapy for 4 cycles. 2. Surgery: One week after the completion of chemotherapy, patients will undergo radical total mesorectal excision surgery. 3. Postoperative Adjuvant Chemotherapy: Starting 3-4 weeks after surgery, patients will resume CAPOX chemotherapy for an additional 4 cycles as adjuvant treatment.

Drug: CAPOX Chemotherapy

Interventions

Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab DRUG

Radiotherapy Protocol: Short-course radiotherapy using three-dimensional conformal or intensity-modulated radiation therapy techniques. The radiation field will be limited to the tumor bed of the primary colon lesion, excluding surrounding draining lymph nodes and enlarged lymph nodes. The dose is fractionated as 5Gy per fraction, for a total of 25Gy over 5 fractions. Titanium clips will be placed on the proximal and distal ends of the colonic lesion via colonoscopy to guide radiation therapy positioning. Chemotherapy Protocol (CAPOX Regimen): 1. Oxaliplatin: 130 mg/m², administered intravenously (ivgtt), on day 1 (d1). 2. Capecitabine: 1000 mg/m², orally (po), twice daily (bid), from day 1 to day 14 (d1-14). Immunotherapy Protocol: During preoperative treatment, Sintilimab (immune checkpoint inhibitor) will be administered concurrently with each chemotherapy cycle.

Node-Sparing Short-Course Radiotherapy Combined with CAPOX and Sintilimab

CAPOX Chemotherapy DRUG

Participants will receive 4 cycles of CAPOX chemotherapy followed by radical total mesorectal excision surgery, and then 4 additional cycles of postoperative CAPOX chemotherapy.

Preoperative CAPOX Regimen as Neoadjuvant Therapy

Eligibility Criteria

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

You may qualify if:

• \. Patients willing to undergo neoadjuvant treatment. 2. Age ≥ 18 years. 3. Tumor confirmed by colonoscopy and enhanced abdominal CT to be ≥ 12 cm from the anal verge.
• \. Histologically diagnosed adenocarcinoma; genetic testing indicates MSI-L or MSS, or immunohistochemistry from tumor biopsy shows pMMR (all four proteins-MSH1, MSH2, MSH6, and PMS2-are positive).
• \. Clinical staging by enhanced abdominal CT evaluates as cT3-4N0-2M0. 6. ECOG performance status score of 0-1. 7. No prior treatment with anti-tumor, immunotherapy, or abdominal radiation therapy before enrollment.
• \. Blood test results (without transfusion within 14 days and no use of granulocyte colony-stimulating factor or other hematopoietic stimulators within 7 days before the lab test):
• White blood cell count ≥ 3.5 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin concentration ≥ 9 g/dL;
• Liver function tests (bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 5 × ULN);
• Renal function (serum creatinine ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min);
• Coagulation (INR ≤ 1.5 × ULN, PT and APTT ≤ 1.5 × ULN);
• Thyroid function: TSH ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4 levels must be evaluated, and if FT3 and FT4 are normal, the patient is eligible.
• \. Voluntary participation with a signed informed consent form.

You may not qualify if:

• \. History of other malignancies within the past 5 years. 2. Patients with metastases in other locations (stage IV). 3. Patients with MSI-H or dMMR. 4. Patients with conditions such as bowel obstruction, perforation, or bleeding requiring emergency surgery.
• \. Known allergy to the study drug or any of its excipients. 6. Patients with any unstable systemic diseases, including but not limited to severe infections, uncontrolled diabetes, uncontrolled hypertension, unstable angina, cerebrovascular accidents or transient ischemic attacks, myocardial infarction, congestive heart failure, or severe illnesses requiring medication (such as arrhythmias, liver, kidney, or metabolic diseases) that are life-threatening.
• \. History of active autoimmune diseases requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within the last 2 years. Replacement therapies (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic treatments.
• \. Known history of HIV infection or acquired immunodeficiency syndrome (AIDS). 9. Receipt of any investigational drug (including immunotherapy) or participation in another interventional clinical study within 30 days before screening.
• \. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study; men or women unwilling to use effective contraception during the study.
• \. Vulnerable populations, including those with mental illness, cognitive impairment, or critically ill patients.
• \. Any other conditions deemed inappropriate for participation by the investigator.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (2)

Sir Run Run Shaw Hospital, Zhejiang University

Hangzhou, China, 310016, China

Location

Sir Run Run Shaw Hospital, Zhejiang University

Hangzhou, Zhejiang, 310016, China

Location

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MeSH Terms

Conditions

Spinocerebellar Degenerations; Colonic Neoplasms

Interventions

sintilimab

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Central Study Contacts

Zhangfa Song, Ph.D.;M.D.

CONTACT

+86 13867421652; songzhangfa@zju.edu.cn

Engeng Chen, M.D.

CONTACT

+86 15258672303; chenengeng@zju.edu.cn

Study Design

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

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: October 1, 2024
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)