an open-label, multicenter, single-arm clinical study on the use of doxorubicin liposome in combination with capox and bevacizumab regimen for first-line treatment of advanced colorectal adenocarcinoma with smad4r361h/c mutation.

Conditions: Advanced Colorectal Adenocarcinoma

Summary: this is a prospective, single-arm clinical study designed to evaluate the 6-month progression-free survival rate (6-month pfs rate) of doxorubicin liposome combined with capox and bevacizumab regimen as first-line treatment for advanced colorectal adenocarcinoma with smad4r361h/c mutation. the study plans to recruit 13 patients. after receiving 8 cycles of induction therapy, patients whose efficacy is evaluated as complete response (cr), partial response (pr), or stable disease (sd) (according to recist 1.1) will enter maintenance therapy.


Eligibility criteria:
inclusion criteria: 1. the patient voluntarily participates in the study, signs the informed consent form, and demonstrates good compliance; 2. age 18 years or older (inclusive), regardless of gender; 3. histologically and/or cytologically confirmed unresectable colorectal adenocarcinoma; 4. for left-sided colon cancer or rectal cancer patients, must be non-ras wild-type; 5. non-dmmr/msi-h; 6. smad4r361h/c mutation; 7. no prior history of systemic chemotherapy; 8. ecog performance status of 0 or 1; 9. hematological tests (within 14 days without blood transfusion): neutrophil absolute count ≥ 1.5 × 10⁹/l, platelet count ≥ 100 × 10⁹/l, hemoglobin ≥ 90 g/l; 10. liver function tests (ast and alt ≤ 3 × uln, bilirubin ≤ 1.5 × uln; if liver metastasis is present, ast and alt ≤ 5 × uln); 11. renal function (serum creatinine ≤ 1.5 × uln or creatinine clearance (ccr) ≥ 60 ml/min); 12. both male and female subjects of reproductive age must use effective contraception. exclusion criteria: 1. patients with known contraindications to doxorubicin liposome, oxaliplatin, capecitabine, or bevacizumab; 2. patients who have received radiotherapy or any anti-tumor treatments (chemotherapy, targeted therapy, immunotherapy, radiofrequency ablation, traditional chinese medicine with anti-tumor indications, immunomodulators, or tumor embolization, etc.); 3. patients who have had other malignancies within the past 5 years or have concurrent malignancies (except for cured skin basal cell carcinoma and carcinoma in situ of the cervix); 4. patients who have experienced significant clinical bleeding symptoms, obvious bleeding tendency, or hemoptysis within 3 months prior to treatment, or who have had venous/thrombotic events such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism within the previous 6 months; or require long-term anticoagulation treatment with warfarin or heparin, or require long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day); 5. patients with active cardiovascular diseases within 6 months before treatment, including myocardial infarction, severe/uncontrolled angina. echocardiography showing left ventricular ejection fraction \<50%, or poorly controlled arrhythmia; 6. known history of primary immunodeficiency virus infection; 7. patients with active or uncontrolled severe infections; 8. any other disease, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory test abnormalities, and based on the investigator's judgment, there is reasonable suspicion that the patient has a condition or disease that is unsuitable for the use of the study drug; 9. any situation that, in the investigator's opinion, could pose a risk to the patient receiving study drug treatment, interfere with the assessment of the study drug's safety, or affect the interpretation of results.