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

NCT06949111 | Recruiting Phase 2

• 1 other identifier: 2025044
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Can the combination of radiotherapy and systemic treatment improve the R0 resection rate and complete response (CR) rate compared to chemotherapy alone?
2. 2.Does this combination therapy enhance the tumor immune microenvironment, leading to better long-term outcomes?
3. 3.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.
4. 4.Receive 4 cycles of CAPOX in the control group.
5. 5.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.

Conditions

Colon Cancer

Keywords

Locally advanced colon cancer; Neoadjuvant chemoradiotherapy; Immune checkpoint inhibitors; Complete response rate; Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Tumor Complete Response (CR) Rate

  CR including pCR and cCR

  2 years

Secondary Outcomes (6)

• MPR rate

  4 years

• R0 Resection Rate

  4 years

• Adjacent Organ Preservation Rate

  4 years

• EFS rate

  3 years

• OS rate

  3 years

Study Arms (2)

Radiotherapy + Systemic Therapy

EXPERIMENTAL

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.

Radiation: radiotherapy; Drug: CAPOX; Drug: Capecitabine; Drug: Iparomlimab and Tuvonralimab Injection

Chemotherapy Alone

ACTIVE COMPARATOR

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

Interventions

radiotherapy RADIATION

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).

Radiotherapy + Systemic Therapy

CAPOX DRUG

4 cycles, Oxaliplatin 130 mg/m², Capecitabine 825 mg/m²

Chemotherapy Alone; Radiotherapy + Systemic Therapy

Capecitabine DRUG

Administer Capecitabine at a dose of 825 mg/m², twice daily, orally on radiotherapy days

Radiotherapy + Systemic Therapy

Iparomlimab and Tuvonralimab Injection DRUG

IV, 5 mg/kg every 3 weeks

Radiotherapy + Systemic Therapy

Eligibility Criteria

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

You may qualify if:

• 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).
• Women of childbearing potential and men must agree to use effective contraception during the study and for 6 months after the last treatment.
• Willingness to sign a written informed consent form and commit to completing the entire treatment and follow-up plan.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hebei Medical University Fourth Hospital: lead

Study Sites (1)

the Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Radiotherapy; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Fengpeng Wu

CONTACT

15032818011; wfpzhj@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: April 29, 2025
• Study Start: May 15, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: July 1, 2025

Record last verified: 2025-04

Locations

CN (1)