Clinical trial NCT06882915: Efficacy and Safety of Trifluridine/tipiracil (TAS-102) Combined with Bevacizumab and Putalimab in the Treatment of Patients with MCRC After Cytoreductive Surgery: a Single-arm, Single-center Clinical Study
Official title: Efficacy and Safety of Trifluridine/tipiracil (TAS-102) Combined with Bevacizumab and Putalimab in the Treatment of Patients with MCRC After Cytoreductive Surgery: a Single-arm, Single-center Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer (CRC)
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2025-03-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The treatment regimen is trifluridine/tipirimidine (TAS-102) combined with bevacizumab and putelimab, with a 28-day medication cycle.

TAS-102: Use at the recommended dose of 35 mg/m² each time, twice a day from the 1st to the 5th day and the 8th to the 12th day every 28 days, with meals.

Bevacizumab: Once a day on the 1st and 15th day every 28 days, at the recommended dose of 5 mg/kg each time, with meals.

Putelimab: According to the recommended dose of 200 mg/time, intravenous drip, infusion time is 60 minutes, once every 28 days.
Primary purpose: TREATMENT

Brief summary: 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 criteria: Inclusion Criteria:

* 1. After complete cytoreduction surgery (CC0) for peritoneal metastasis of colorectal cancer;
* 2. Patients diagnosed with peritoneal metastasis of colorectal cancer by pathology and imaging;
* 3. Microsatellite stable (MSS) by genetic testing;
* 4. Expected survival time at least 6 months;
* 5. ECOG (Eastern Cooperative Oncology Group) performance status score of 0 or 1;
* 6. Normal function of the heart, liver and kidneys;
* 7. Normal hematological indicators: neutrophil count ≥1.5×109/L, white blood cell count (WBC) ≥3.0×109/L, hemoglobin ≥10g/dL, platelet count ≥100×109/L;
* 8. Normal biochemical indicators: total bilirubin ≤1.5×upper limit of normal (ULN), AST and ALT ≤2.5 times upper limit of normal, serum creatinine and urea nitrogen (BUN) ≤1.5 times the upper limit of normal value;

Exclusion Criteria:

* 1. Unwilling to sign the informed consent form;
* 2. Currently participating in interventional research treatment, or receiving other drugs or research devices within 4 weeks before enrollment;
* 3. Having other malignant tumors at the same time;
* 4. Other serious diseases that the investigators judge may affect follow-up and short-term survival;
* 5. Allergic to TAS-102, bevacizumab or putelimab components;
* 6. Uncontrolled brain metastases;
* 7. Pregnant or lactating women;
* 8. Those with a history of mental illness;
* 9. Uncontrolled complications including but not limited to active infection, symptomatic congestive heart failure, unstable angina, arrhythmia;
* 10. Severe coronary artery disease or cerebrovascular disease, or other diseases that the investigators believe are not suitable for enrollment;

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: Two Years
Secondary outcomes:
measure: Objective Remission Rate (ORR)
timeFrame: Two Years
measure: Overall Survival (OS)
timeFrame: Two Years
measure: Treatment response
timeFrame: Two Years
measure: Incidence rate of adverse events
timeFrame: Baseline before any treatment,3 months after any treatment
Other outcomes:
Locations:
Study officials:
References: