Combining trifluridine/tipiracil with oxaliplatin and bevacizumab for advanced colorectal cancer

Trifluridine/Tipiracil Combined With Oxaliplatin and Bevacizumab Versus XELOX Plus Bevacizumab in the First-line Treatment of Advanced Colorectal Cancer (TOBACO): a Randomized, Controlled, Phase II Study

This study is testing a new combination of medications for advanced colorectal cancer to see if it works better than the standard treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 184 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: chemotherapy, bevacizumab
• Locations: 1 site (Tianjin)
• Trial ID: NCT05077839 on ClinicalTrials.gov

What this trial studies

This clinical trial compares the safety and efficacy of a new treatment regimen combining trifluridine/tipiracil with oxaliplatin and bevacizumab against the standard XELOX plus bevacizumab for patients with advanced colorectal cancer. It is a randomized, parallel-group study involving 184 participants who will be assigned to one of the two treatment groups after providing informed consent. The experimental group will receive trifluridine/tipiracil orally along with oxaliplatin and bevacizumab, while the control group will receive the standard XELOX regimen with bevacizumab. The study aims to evaluate the effectiveness of the new combination in the first-line treatment setting.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed colonic adenocarcinoma who have not received prior chemotherapy for advanced disease.

Not a fit: Patients with prior chemotherapy for advanced colorectal cancer or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a more effective first-line option for patients with advanced colorectal cancer.

How similar studies have performed: Other studies have shown promise with similar combinations, but this specific approach is being evaluated for the first time in this context.

Eligibility criteria

Inclusion Criteria:

1. Signed the informed consent.
2. Age ≥18.
3. Colonic adenocarcinoma confirmed histologically or histopathologically.
4. No previous chemotherapy for advanced colorectal cancer, or patients who had received adjuvant chemotherapy after radical resection and relapsed 12 months after the completion of adjuvant chemotherapy.
5. ECOG physical status score is 0 or 1.
6. There are measurable metastatic lesions according to RECIST version 1.1.
7. Appropriate organ function according to the following laboratory test values obtained within 7 days prior to use on Day 1 of Cycle 1:

   1. Hemoglobin value ≥9.0g/dL.
   2. Absolute neutrophil count ≥1,500/mm3 (≥1.5\*109/L).
   3. Platelet count ≥100,000/mm3 (≥100\*109/L).
   4. Total serum bilirubin ≤1.5\* upper normal limit (ULN).
   5. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5\* upper limit of normal value (ULN). If the abnormal liver function is due to liver metastasis, AST and ALT should be ≤5\*ULN.
   6. Serum creatinine ≤1.5 times \* upper limit of normal (ULN) or creatinine clearance ≥50ml/min.
8. The results of urine or serum pregnancy test within 7 days prior to treatment were negative. Women who are likely to become pregnant and men must agree to take adequate contraceptive measures during the study period until 6 months after the end of medication.
9. Survival is expected to be at least 3 months.
10. Willing and able to follow research procedures and visit plans.

Exclusion Criteria:

1. Has a serious illness or medical condition, including but not limited to the following:

   1. There are other active malignant tumors at the same time, excluding those that have not occurred for more than 5 years or carcinoma in situ that can be cured by adequate treatment.
   2. Known presence of brain metastases or leptomeningeal metastases.
   3. Systemic active infection (i.e., infection causes body temperature ≥38℃).
   4. Clinically significant intestinal obstruction, pulmonary fibrosis, renal failure, liver failure, or symptomatic cerebrovascular disease.
   5. Uncontrolled diabetes.
   6. Severe/unstable angina, New York Heart Association (NYHA) grade III or IV symptomatic congestive heart failure.
   7. Gastrointestinal bleeding of clinical significance.
   8. Known presence of human immunodeficiency virus (HIV) or acquired routine immunodeficiency syndrome (AIDS) -associated disease, or active hepatitis B or C.
   9. There are psychiatric disorders that may increase the risk associated with participating in the study or taking the study drugs, or may interfere with the interpretation of the study results.
2. Any of the following treatments were received within a specific time frame before the study drug was taken:

   1. Major surgery in the previous 4 weeks. (Major surgery refers to laparotomy, thoracotomy, and laparoscopic resection of internal organs. On-off of abdomen was excluded)
   2. Radiotherapy with extended field within the previous 4 weeks or radiotherapy with limited field within the previous 2 weeks.
   3. Any investigational drugs within the previous 4 weeks.
3. Presence of neurotoxicity of CTCAE grade 2 or above caused by adjuvant therapy.
4. Pregnant or lactating women.
5. The researcher did not consider it appropriate to enter the study.

Where this trial is running

Tianjin

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, China (Recruiting)

Study contacts

• Principal investigator: Yi Ba, MD — Tianjin Medical University Cancer Institute and Hospital
• Study coordinator: Yi Ba, MD

Conditions First-line Treatment; Advanced Colorectal Cancer; Trifluridine/tipiracil; first-line treatment; advanced colorectal cancer