Combining radiotherapy and systemic therapy for advanced colon cancer

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）

This study is testing whether combining radiation therapy with chemotherapy and immune treatments can help people with advanced colon cancer have better surgery outcomes and improve their overall health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 128 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hebei Medical University Fourth Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, Iparomlimab, Tuvonralimab
• Locations: 1 site (Shijiazhuang, Hebei)
• Trial ID: NCT06949111 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of combining radiotherapy with systemic treatment, including chemotherapy and immune checkpoint inhibitors, for patients with pMMR/MSS T4M0 stage colon cancer. The study aims to determine if this combination improves the R0 resection rate and complete response rate compared to chemotherapy alone. Participants will receive concurrent chemoradiotherapy followed by cycles of CAPOX and immune checkpoint inhibitors. The trial will assess the impact of this approach on the tumor immune microenvironment and long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed pMMR/MSS T4M0 colon adenocarcinoma and an ECOG performance status of 0-1.

Not a fit: Patients with non-pMMR/MSS colon cancer or those with significant comorbidities affecting treatment tolerance may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve surgical outcomes and long-term survival for patients with advanced colon cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of radiotherapy and immunotherapy, indicating potential for success in this approach.

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.

Where this trial is running

Shijiazhuang, Hebei

• the Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (Recruiting)

Study contacts

• Study coordinator: Fengpeng Wu

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