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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:
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Complete Response (CR) Rate | CR including pCR and cCR | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| MPR rate | 4 years | |
| R0 Resection Rate | 4 years | |
| Adjacent Organ Preservation Rate |
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Inclusion Criteria:
(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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fengpeng Wu | Contact | 15032818011 | wfpzhj@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the Fourth Hospital of Hebei Medical University | Recruiting | Shijiazhuang | Hebei | 050000 | China |
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| ID | Term |
|---|---|
| D003110 | Colonic Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| CAPOX | Drug | 4 cycles, Oxaliplatin 130 mg/m², Capecitabine 825 mg/m² |
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| Capecitabine | Drug | Administer Capecitabine at a dose of 825 mg/m², twice daily, orally on radiotherapy days |
|
| Iparomlimab and Tuvonralimab Injection | Drug | IV, 5 mg/kg every 3 weeks |
|
| 4 years |
| EFS rate | 3 years |
| OS rate | 3 years |
| Adverse events | 4 years |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |