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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Colorectal Adenocarcinoma
• Intervention / Treatment: Drug: Doxorubicin liposome combined with CapOX and Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 13
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: shi min MD,PHD; Phone Number: 86-20-62787731; Email: nfyyshimin@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxorubicin liposome combined with CapOX and Bevacizumab regimen as first-line treatment; 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.	Drug: Doxorubicin liposome combined with CapOX and Bevacizumab; Bevacizumab (7.5 mg/kg, IV, Day 1) + Oxaliplatin (130 mg/m², IV, Day 1) + Capecitabine (1000 mg/m², oral, twice daily, for 14 days) + Doxorubicin liposome (20 mg/m², IV, Day 1), repeated every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month progression-free survival (PFS)	Defined as the time between the first occurrence of disease progression (PD) or death after the patient receives the study drug, whichever occurs first.	3 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: NFEC-2024-310

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No