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

Official title

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）

Overview

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.

Interventions

• 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).
• 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

Primary outcome measures

• Tumor Complete Response (CR) Rate [Time frame: 2 years]

Secondary outcome measures (6)

• MPR rate [Time frame: 4 years]
• R0 Resection Rate [Time frame: 4 years]
• Adjacent Organ Preservation Rate [Time frame: 4 years]
• EFS rate [Time frame: 3 years]
• OS rate [Time frame: 3 years]
• Adverse events [Time frame: 4 years]

Eligibility criteria

Inclusion criteria

• Age ≥18 years, no restriction on gender.
• ECOG performance status of 0-1.
• 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).
• Baseline imaging (enhanced CT/MRI) confirms clinical staging as cT4NanyM0 according to the AJCC 8th edition staging criteria.
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Fourth Hospital of Hebei Medical University — Shijiazhuang

Identifiers

NCT: NCT06949111 · 2025044

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗