Radiotherapy + Systemic Therapy as Conversion Therapy for pMMR/MSS T4M0 Colon Cancer（Neo-Color）

Efficacy and Safety of Conversion Therapy for pMMR/MSS T4M0 Colon Cancer Patients Treated With Radiotherapy and Systemic Therapy: a Prospective, Open-label, Multi-center, Randomized Controlled Trial（Neo-Color）

The goal of this clinical trial is to evaluate the efficacy and safety of conversion therapy using radiotherapy combined with systemic treatment (chemotherapy + immune checkpoint inhibitors) for patients with pMMR/MSS T4M0 stage colon cancer. The main questions it aims to answer are:

1. Can the combination of radiotherapy and systemic treatment improve the R0 resection rate and complete response (CR) rate compared to chemotherapy alone?
2. Does this combination therapy enhance the tumor immune microenvironment, leading to better long-term outcomes?

Researchers will compare the experimental group receiving concurrent chemoradiotherapy (CCRT) followed by 4 cycles of CAPOX + Iparomlimab and Tuvonralimab Injection with the control group receiving 4 cycles of CAPOX alone to see if the combination therapy offers superior efficacy.

Participants will:

1. Undergo preoperative CCRT combined with one cycle of Iparomlimab and Tuvonralimab Injection, followed by 4 cycles of CAPOX + Iparomlimab and Tuvonralimab Injection in the experimental group.
2. Receive 4 cycles of CAPOX in the control group.
3. After the initial treatment regimen, surgical candidates will undergo surgery followed by an additional 4 cycles of CAPOX. Non-surgical candidates will continue with 4 more cycles of CAPOX, completing a total of 8 cycles. Efficacy will be re-evaluated after the completion of 8 cycles.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: CAPOX; Drug: Capecitabine; Drug: Iparomlimab and Tuvonralimab Injection; Radiation: radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fengpeng Wu; Phone Number: 15032818011; Email: wfpzhj@126.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Fengpeng Wu; Phone Number: 15032818011; Email: wfpzhj@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years, no restriction on gender.
2. ECOG performance status of 0-1.
3. Histopathologically confirmed diagnosis of colon adenocarcinoma (including mucinous adenocarcinoma), identified as pMMR/MSS type; the primary tumor site must be specified (left colon defined as from the splenic flexure to the rectosigmoid junction, right colon defined as from the cecum to the proximal splenic flexure).
4. Baseline imaging (enhanced CT/MRI) confirms clinical staging as cT4NanyM0 according to the AJCC 8th edition staging criteria.
5. Laboratory criteria prior to enrollment must meet the following ranges:

(1) Hematology: Absolute neutrophil count ≥ 1.5 × 10^9/L, platelets ≥ 100 × 10^9/L, hemoglobin ≥ 90 g/L.

(2) Liver and renal function: ALT/AST ≤ 2.5 × ULN, total bilirubin ≤ 1.5 × ULN, creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 mL/min (Cockcroft-Gault formula).

(3) Coagulation function: INR ≤ 1.5, APTT ≤ 1.5 × ULN (for those not on anticoagulation therapy).

6.Women of childbearing potential and men must agree to use effective contraception during the study and for 6 months after the last treatment.

7.Willingness to sign a written informed consent form and commit to completing the entire treatment and follow-up plan.

Exclusion Criteria:

1. Histological type of neuroendocrine carcinoma, squamous cell carcinoma, or other non-adenocarcinoma components comprising more than 50%.
2. Presence of distant metastasis (including peritoneal metastasis, non-regional lymph node metastasis, or organ metastasis).
3. Previous radiotherapy, chemotherapy, targeted therapy, or immunotherapy for colon cancer.
4. Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy).
5. Active infections (e.g., HIV, positive HBV/HCV viral load requiring antiviral treatment for stabilization).
6. Severe cardiovascular diseases (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension >160/100 mmHg).
7. History of other malignancies (except for cured non-melanoma skin cancer, cervical carcinoma in situ, etc., with a disease-free period of ≥5 years).
8. Uncontrolled diabetes (HbA1c > 8%) or thyroid dysfunction (TSH outside the normal range requiring medication).
9. Severe chronic bowel diseases (e.g., active Crohn's disease, ulcerative colitis).
10. History of radiation enteritis or extensive abdominal adhesions affecting radiotherapy target delineation.
11. Unrecovered bone marrow suppression (ANC < 1.5 × 10^9/L, PLT < 100 × 10^9/L, Hb < 90 g/L).
12. Liver function with Child-Pugh score ≥ B or renal function with eGFR < 60 mL/min/1.73 m².
13. Pregnant or breastfeeding women (blood/urine HCG test required during screening).
14. Cognitive impairment or history of psychiatric disorders affecting treatment compliance.
15. Concurrent participation in other interventional clinical trials.
16. Patients deemed unsuitable for participation by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemotherapy Alone; Patients will receive 4 cycles of CAPOX. Then all patients were evaluated for therapeutic efficacy 2-3 weeks after therapy. Patients met the criteria for complete remission (cCR) could choose either surgery or not. For patients who chose surgery, four cycles of CAPOX were administered 4-6 weeks after surgery. For patients who did not choose surgery, 4 cycles of CAPOX was continued. For patients did not meet the cCR criteria, surgery and 4 cycles of CAPOX was recommended. Patients who refused surgery continued to receive 4 cycles of CAPOX. If the second response evaluation met the cCR criteria, patients were included in the primary end point.	Drug: CAPOX; 4 cycles, Oxaliplatin 130 mg/m², Capecitabine 825 mg/m²
Experimental: Radiotherapy + Systemic Therapy; Patients undergo radiotherapy (36-41.4 Gy/20-23f). Concurrently, patients will receive Capecitabine (825 mg/m², bid, on radiotherapy days). At 23.4 Gy/13f of radiotherapy, patients will be administered Iparomlimab-Tuvonralimab (5 mg/kg) for one cycle. 1-2 weeks after completing the 36-41.4 Gy radiotherapy, patients will begin 4 cycles of CAPOX plus Iparomlimab-Tuvonralimab (5 mg/kg). All patients were evaluated for therapeutic efficacy 2-3 weeks after above therapy. Patients met the criteria for complete remission (cCR) could choose either surgery or not. For patients who chose surgery, four cycles of CAPOX were administered 4-6 weeks after surgery. For patients who did not choose surgery, 4 cycles of CAPOX was continued. For patients did not meet the cCR criteria, surgery and 4 cycles of CAPOX was recommended. Patients who refused surgery continued to receive 4 cycles of CAPOX. If the second response evaluation met the cCR criteria, patients were included in the primary end point.	Drug: CAPOX; 4 cycles, Oxaliplatin 130 mg/m², Capecitabine 825 mg/m²; Drug: Capecitabine; Administer Capecitabine at a dose of 825 mg/m², twice daily, orally on radiotherapy days; Drug: Iparomlimab and Tuvonralimab Injection; IV, 5 mg/kg every 3 weeks; Radiation: radiotherapy; Radiotherapy: Administer three-dimensional conformal/intensity-modulated/TOMO radiotherapy with a conventional fractionation schedule of 36-41.4 Gy in 20-23 fractions (1.8 Gy per fraction).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Complete Response (CR) Rate	CR including pCR and cCR	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	4 years
MPR rate	4 years
R0 Resection Rate	4 years
Adjacent Organ Preservation Rate	4 years
EFS rate	3 years
OS rate	3 years

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: April 22, 2025
• First Submitted That Met QC Criteria: April 22, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Radiotherapy; Immune checkpoint inhibitors; Locally advanced colon cancer; Neoadjuvant chemoradiotherapy; Complete response rate
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Colonic Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Capecitabine
• Other Study ID Numbers: 2025044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No