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

NCT ID: NCT06949111

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-15
• Study Completion Date: 2029-03-31

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. 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.

Conditions

Colon Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

radiotherapy

Intervention Type: 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).

CAPOX

Intervention Type: DRUG

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

Capecitabine

Intervention Type: DRUG

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

Iparomlimab and Tuvonralimab Injection

Intervention Type: DRUG

IV, 5 mg/kg every 3 weeks

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.

Group Type: ACTIVE_COMPARATOR

CAPOX

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: RADIATION

CAPOX

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

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Iparomlimab and Tuvonralimab Injection

IV, 5 mg/kg every 3 weeks

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hebei Medical University Fourth Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fengpeng Wu

Role: CONTACT

wfpzhj@126.com

15032818011

Facility Contacts

Fengpeng Wu

Role: primary

wfpzhj@126.com

15032818011

Other Identifiers

2025044

Identifier Type: -

Identifier Source: org_study_id