Combining trifluridine/tipiracil with cetuximab for advanced colorectal cancer treatment

Trifluridine/Tipiracil Combined With Cetuximab in the Treatment of Third-line and Above RAS/BRAF Wild-type Metastatic Colorectal Cancer: A Single-center, Prospective Phase Ib/II Study

This study is testing if combining two drugs, trifluridine/tipiracil and cetuximab, can help people with advanced colorectal cancer who have already tried other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: cetuximab, chemotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06379399 on ClinicalTrials.gov

What this trial studies

This is a single-center, prospective, single-arm exploratory study that evaluates the efficacy and safety of trifluridine/tipiracil in combination with cetuximab for patients with third-line and above RAS/BRAF wild-type metastatic colorectal cancer. The study aims to determine how well this combination works in treating patients who have already undergone multiple lines of therapy. Participants will be monitored for treatment response and safety outcomes throughout the study duration.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed metastatic colorectal cancer who have previously received at least second-line treatment and have wild-type RAS/BRAF genes.

Not a fit: Patients with appendiceal or anal canal cancers, or those who have not received prior anti-EGFR therapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with advanced colorectal cancer who have limited treatment choices.

How similar studies have performed: While this approach is exploratory, similar combinations of targeted therapies have shown promise in other studies, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection.
2. Histologically or cytologically confirmed metastatic adenocarcinoma of the colon; excluding appendiceal and anal canal cancers.
3. Previously received at least second-line treatment, including two standard treatment regimens (such as fluoropyrimidine, capecitabine, irinotecan, oxaliplatin with or without anti-VEGF or anti-EGFR agents), if previously received first-line anti-EGFR therapy, achieving at least a partial response (PR) or above, with a discontinuation interval of at least one year.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) (based on RECIST 1.1 criteria, with the longest diameter of tumor lesions on CT/MRI scan ≥10mm, and the shortest diameter of lymph node lesions on CT/MRI scan ≥15mm).
6. Wild-type RAS/BRAF gene detected.
7. Able to take oral medication.
8. Normal organ function, meeting the following criteria within 14 days before treatment initiation:

   * Neutrophil count ≥1.5×10\^9/L;
   * Platelet count ≥75×10\^9/L;
   * Hemoglobin ≥9.0g/dL;
   * Aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN) (or ≤5×ULN if liver metastases);
   * Alanine aminotransferase (ALT) ≤2.5×ULN (or ≤5×ULN if liver metastases);
   * Total bilirubin ≤1.5×ULN;
   * Creatinine clearance (calculated by Cockcroft and Gault formula) \>60mL/min or serum creatinine ≤1.5×ULN;
9. Expected survival time \>3 months (90 days).
10. Women of childbearing potential must have used reliable contraception for 7 days prior to enrollment, have had a negative pregnancy test, and agree to use appropriate contraception methods during the trial and for 6 months after the last dose of investigational drug. Men must agree to use appropriate contraception methods or have undergone surgical sterilization during the trial and for 6 months after the last dose of investigational drug.

Exclusion Criteria:

1. Prior treatment with Trifluridine/Tipiracil;
2. Patients with known dMMR or MSI-H advanced colorectal cancer who have not previously received anti-PD-1 or PD-L1 inhibitors;
3. Participation in another drug clinical trial or receipt of systemic chemotherapy, radiotherapy, or biologic therapy within the past 4 weeks;
4. Known or suspected brain metastases;
5. Synchronous or metachronous cancer with a disease-free survival of ≥5 years (except for colorectal cancer) excluding cured or curatively treated mucosal cancers (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.);
6. Factors significantly affecting oral drug absorption, such as dysphagia, chronic diarrhea, and gastrointestinal obstruction; uncontrolled Crohn's disease or ulcerative colitis;
7. Symptomatic malignant effusion requiring symptomatic treatment (including pleural effusion, ascites, pericardial effusion);
8. Pregnant or lactating women; patients with reproductive potential unwilling or unable to use effective contraceptive measures;
9. Known allergy to the investigational drug, drug class, or its components;
10. Requirement for systemic corticosteroid therapy (excluding local steroids and cetuximab pre-treatment);
11. History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or radiographic evidence of interstitial lung disease;
12. Active local or systemic infections requiring treatment;
13. New York Heart Association (NYHA) functional classification ≥II or severe heart disease;
14. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or history of active hepatitis B or hepatitis C;
15. Unresolved toxicity (CTCAE\>Grade 1) or incomplete recovery from previous cancer surgery.
16. Patients deemed unsuitable for the study by the investigator.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Lv — Zhejiang Cancer Hospital
• Study coordinator: Wangxia Lv

Conditions Colorectal Cancer Metastatic; RAS/BRAF wild-type