Efficacy and Safety of Trifluridine/Tipiracil (TAS-102) Combined With Bevacizumab and Serplulimab in Patients With Metastatic Colorectal Cancer Undergoing Cytoreductive Surgery: A Single-Arm, Single-Center Clinical Study

Phase 1Not Yet RecruitingNCT06882915

Second Affiliated Hospital, Zhejiang University, School of Medicine20 enrolled

Overview

Colorectal cancer (CRC) is one of the most common malignant tumors. With the rapid development of China's economy, people's living standards have been significantly improved, and lifestyles and dietary structures have changed. Smoking, drinking, high-fat, high-energy diets, etc. have led to an increase in the incidence of colorectal cancer year by year. Data show that in 2022, there will be 510,000 new cases of colorectal cancer in China, and about 240,000 deaths related to colorectal cancer. Radical surgery is the main initial treatment for early and middle-stage colorectal cancer and some metastatic colorectal cancer. Although the level of surgical treatment of colorectal cancer has been greatly improved and can achieve cure for some patients, its 5-year overall survival rate is only about 60%, and the main cause of death is distant metastasis and recurrence. In recent years, with the in-depth understanding of the treatment mechanism of metastatic colorectal cancer (mCRC), a variety of new treatment options have been proposed and applied in clinical practice in order to improve the quality of life of patients and prolong their survival. Trifluridine/tipivirine (TAS-102) is a new type of cytotoxic drug that exerts anti-tumor effects by directly incorporating into DNA chains to destroy DNA function. Its mechanism of action is different from that of fluorouracil drugs, and it can resist 5-fluorouracil (5-FU) resistance, providing a new treatment option for mCRC patients. TAS-102 has been approved in China for mCRC patients who have previously received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, as well as those who have previously received or are not suitable for anti-vascular endothelial growth factor (VEGF) therapy and anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type). Bevacizumab, as a monoclonal antibody targeting VEGF, exerts its anti-tumor effect by inhibiting tumor angiogenesis. Putlimumab, as an immune checkpoint inhibitor, enhances the body's immune response to tumors by blocking the PD-1/PD-L1 signaling pathway. Combination therapy has attracted much attention due to its possible synergistic effect. Studies have shown that TAS-102 combined with bevacizumab can achieve longer overall survival (OS) than TAS-102 monotherapy. In addition, TAS-102 combined with bevacizumab for refractory mCRC has also been approved by the FDA, showing its potential and importance in the treatment of mCRC. Therefore, this study aims to explore the efficacy and safety of TAS-102 combined with bevacizumab and putelimab in patients with mCRC after cytoreductive surgery, in order to provide a more effective treatment for mCRC patients. Through the design of a single-arm, single-center clinical study, we can have a deeper understanding of the efficacy and safety of this combined treatment in a specific patient population, providing a scientific basis for future clinical applications.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Patients who had undergone cytoreductive surgery (CC0-1) for colorectal cancer with peritoneal metastases; 2. Patients with extra-peritoneal metastatic lesions that were unlikely to affect prognosis in the short term; 3. Patients who had failed standard therapies (disease progression or intolerance to oxaliplatin, irinotecan, fluorouracil, or other chemotherapeutic agents) or for whom no effective treatment options were available; 4. Patients with histologically and radiologically confirmed peritoneal metastasis from colorectal cancer, with microsatellite stable (MSS) status as determined by genetic testing; 5. Age ≥ 18 years at the time of informed consent; 6. Estimated life expectancy \> 6 months; 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 8. Adequate function of major organs (cardiac, hepatic, and renal); 9. Adequate hematological parameters: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, white blood cell count (WBC) ≥ 3.0 × 10⁹/L, hemoglobin ≥ 10 g/dL, and platelet count ≥ 100 × 10⁹/L; 10. Adequate biochemical parameters: total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; serum creatinine and blood urea nitrogen (BUN) ≤ 1.5 × ULN; 11. Ability to comply with the study protocol and follow-up procedures. Exclusion Criteria: 1. Refusal to provide informed consent; 2. Currently participating in an interventional clinical study, or having received other investigational drugs or devices within 4 weeks prior to enrollment; 3. Concurrent malignancy, except for malignancies that have been clinically cured; 4. Other severe diseases that, in the investigator's judgment, may affect follow-up compliance or short-term survival; 5. Known hypersensitivity to any component of TAS-102, bevacizumab, or serplulimab; 6. Uncontrolled brain metastases; 7. Active autoimmune disease; 8. Pregnant or lactating women; 9. History of psychiatric disorders; 10. Uncontrolled comorbidities including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, severe coronary artery disease, or cerebrovascular disease, or any other condition deemed by the investigator to render the patient ineligible for enrollment; 11. Any other condition that the investigator considers unsuitable for enrollment.

Outcomes

Primary Outcomes

Progression-free survival (PFS)

The period from the beginning of treatment to the first occurrence of disease progression or death from any cause. If such situation is not met, the last evaluation date shall be used for analysis. In addition, if the treatment is terminated without confirming the progress of the disease, the imaging examination and follow-up should also be carried out after the treatment is terminated.

Time frame: Two Years

Secondary Outcomes

Objective Remission Rate (ORR)

The proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit. The remission period usually refers to the period from the beginning of curative effect to the confirmation of tumor progression. The objective response rate is generally defined as the sum of complete response plus partial response (CR+PR).

Time frame: Two Years

Overall Survival (OS)

The time from the date of treatment to the date of death due to any reason. For patients who survived in the final analysis, the date of the last contact will be recorded.

Time frame: Two Years

Treatment response

To evaluate tumor response using imaging examinations (CT/MRI) and tumor shrinkage rate using the response evaluation criteria in solid tumors (RECIST 1.1).

Time frame: Two Years

Incidence rate of adverse events

According to NCI CTCAE v5.0

Time frame: Baseline before any treatment,3 months after any treatment

Efficacy and Safety of Trifluridine/Tipiracil (TAS-102) Combined With Bevacizumab and Serplulimab in Patients With Metastatic Colorectal Cancer Undergoing Cytoreductive Surgery: A Single-Arm, Single-Center Clinical Study

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes