colorectal cancer
Conditions
Interventions
Experimental group:Trifluridine/Tipiracil (TAS-102) + Bevacizumab Group + Low-Dose Radiotherapy (LDRT) + PD-1 Inhibitor:The radiation therapy for the patients will start on Day 1, with 2 Gy per sessio
control group:Orally administer Trifluridine/Tipiracil (TAS-102) at the recommended dose according to the package insert.
Sponsors
Mianyang 404 Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. All participants must sign an informed consent form before starting any study-related procedures and must be able to comply with the study visit schedule and related protocols. 2. Age:>=18 years old. 3. Diagnosed with metastatic, unresectable MSS/pMMR colon or rectal adenocarcinoma by cytology or histology; disease progression after no more than two prior chemotherapy regimens, or intolerance to the last regimen. Previous treatments must include fluoropyrimidines, irinotecan, oxaliplatin, anti-VEGF monoclonal antibodies, or anti-EGFR monoclonal antibodies (RAS wild-type). 4. Willing to provide tumor tissue samples, which may be archival or freshly obtained, for biomarker testing, immunohistochemistry, and/or PCR and next-generation sequencing to assess microsatellite status, and RAS and BRAF amplification status. 5. At least one measurable lesion according to the RECIST v1.1 criteria. 6. ECOG Performance Status: 0-1. 7. Expected survival >3 months. 8. Participants must meet the following requirements: 1) Hematology: - White blood cell count >= 3.5 × 10^9/L - Absolute neutrophil count (ANC) >= 1.5 × 10^9/L - Platelets (PLT)>= 90 × 10^9/L - Hemoglobin (HGB) >= 9 g/dL 2) Liver Function: - Total bilirubin (TBIL) = 50 mL/min (calculated using the Cockcroft/Gault formula): - Female: CrCl = (140 - age) × weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)) - Male: CrCl = (140 - age) × weight (kg) / (72 × serum creatinine (mg/dL)) 4) Coagulation Function: - International normalized ratio (INR) = 50% - QTcF interval<= 450 ms 9. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, participants with normal total T3 (or FT3) and FT4 levels may still be eligible for inclusion. 10. Toxicity from previous treatments (except for hair loss) must be <= Grade 1 or returned to baseline levels. 11. The investigator must judge that the participant is compliant and able to complete scheduled visits, treatments, and laboratory tests according to the protocol. Radiation oncology specialists must evaluate the absence of severe pulmonary ventilation dysfunction and acute heart failure, confirming no contraindications for radiotherapy. Participants must agree to receive immunotherapy and radiotherapy. 12.Female participants of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first dose of study drug (Cycle 1, Day 1). If the urine pregnancy test is inconclusive, a serum pregnancy test must be performed. Women of non-childbearing potential are defined as those who are at least one year post-menopausal or have undergone surgical sterilization or hysterectomy. If there is a risk of pregnancy, all participants (male or female) must use contraception with a failure rate of less than 1% during the entire treatment period and for 120 days after the last dose of the study drug or 180 days after the last chemotherapy dose.
Exclusion criteria
Exclusion criteria: 1.Participants who have previously received treatment with regorafenib or immune checkpoint inhibitors for cancer. 2.Participants with unknown RAS status. 3.Exclusion of participants with active CNS metastases (including but not limited to carcinomatous meningitis, spinal cord compression). However, if CNS metastases have been adequately treated and neurological symptoms have resolved to baseline levels at least 2 weeks before enrollment (excluding residual signs or symptoms related to CNS treatment), participants may be included. In addition, participants must have discontinued corticosteroids at least 4 weeks prior to enrollment. 4.Participants with tumor-related emergencies that require immediate treatment. 5.Participants with peripheral neuropathy. 6.Participants with significant coagulation abnormalities or those receiving thrombolytic or anticoagulant therapy. 7.Participants who have required systemic corticosteroids (equivalent to >10 mg of prednisone/day) or other immunomodulators (e.g., interleukin-2, IFN-a, IFN-?, cyclosporine, G-CSF, mTOR inhibitors) within 28 days before the study treatment. Participants using inhaled or topical corticosteroids, or those on adrenal corticosteroid replacement therapy equivalent to 140/100 mmHg, based on an average of three consecutive measurements). - Clinically significant arrhythmias, atrial fibrillation, and/or conduction abnormalities (within 6 months prior to screening) or current evidence of congenital long QT syndrome, >=2nd-degree complete heart block, or hypokalemia >=CTCAE Grade 3. - History of acute coronary syndrome (within 6 months prior to screening), or current evidence of myocardial infarction, unstable angina, coronary artery bypass grafting (CABG), coronary angioplasty, or stent placement. - Complete left bundle branch block, right bundle branch block + left anterior fascicular block (LAHB), or dual bundle branch block. 9. Participants with clinically significant third-space fluid accumulation, such as pericardial effusion, pleural effusion, or ascites, which cannot be controlled by drainage or other treatments. 10.Participants with known allergies to the study drugs or excipients, or a history of severe allergic reactions to any monoclonal antibody. 11. Participants who have experienced a severe infection within 4 weeks prior to starting study treatment, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia. Participants who received therapeutic oral or intravenous antibiotics within 2 weeks prior to starting the study treatment may be excluded. Participants receiving prophylactic antibiotics (e.g., for urinary tract infections or chronic obstructive pulmonary disease exacerbations) are eligible. 12.Participants with known or suspected active autoimmune diseases (congenital or acquired), such as interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. (Participants with vitiligo or childhood asthma that has completely resolved without the need for intervention in adulthood, and well-controlled type 1 diabetes, are eligible). 13.Participants who
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Disease Control Rate;Duration of Response;Six-Month Progression-Free Survival Rate;Overall Survival; | — |
Countries
CHINA
Contacts
Public Contactsuzhou
Mianyang 404 Hospital
Outcome results
None listed