Clinical trial NCT06949111: Radiotherapy + Systemic Therapy as Conversion Therapy for pMMR/MSS T4M0 Colon Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colon Cancer
Keywords: Locally advanced colon cancer
Neoadjuvant chemoradiotherapy
Immune checkpoint inhibitors
Complete response rate
Radiotherapy
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2025-04-29
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 75 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.

Primary outcomes:
measure: Tumor Complete Response (CR) Rate
timeFrame: 2 years
Secondary outcomes:
measure: MPR rate
timeFrame: 4 years
measure: R0 Resection Rate
timeFrame: 4 years
measure: Adjacent Organ Preservation Rate
timeFrame: 4 years
measure: EFS rate
timeFrame: 3 years
measure: OS rate
timeFrame: 3 years
measure: Adverse events
timeFrame: 4 years
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: the Fourth Hospital of Hebei Medical University
state: Hebei
Study officials:
References: