Trifluridine/Tipiracil Combined With Cetuximab in the Treatment of Third-line and Above RAS/BRAF Wild-type mCRC

NCT ID: NCT06379399

Last Updated: 2024-04-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-30
• Study Completion Date: 2025-12-31

Brief Summary

This study is a single-center, prospective, single-arm exploratory study aimed at evaluating the efficacy and safety of trifluridine/tipiracil in combination with cetuximab in the treatment of third-line and above RAS/BRAF wild-type metastatic colorectal cancer.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuximab Combined With Trifluridine/Tipiracil

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks;

Trifluridine/Tipiracil

Intervention Type: DRUG

Phase I:

1. 6 patients (male and female) will be enrolled to evaluate safety. Patients will receive Trifluridine/Tipiracil at a dose of 35mg/m2 (maximum single dose of 80 mg). Patients will be followed up for Dose-Limiting Toxicities (DLTs) (2 Cycles, Day 1-Day 28). If ≤2 patients experience DLTs (2 Cycles, Day 1-Day 28), the study will proceed to Phase II with a dose of 35mg/m2. If ≥3 patients experience DLTs (2 Cycles, Day 1-Day 28), the study will proceed to Phase II with a dose of 30mg/m2.

2. Based on the results of the 35mg/m2 dose group, 6 patients (male and female) will be enrolled in the 30mg/m2 dose group to evaluate safety. Patients will be followed up for DLTs (2 Cycles, Day 1-Day 28). If ≤2 patients experience DLTs (1 Cycle, Day 1-Day 28), the study will proceed with a dose of 30mg/m2 in Phase II.

Phase II:

Trifluridine/Tipiracil: po, twice daily from Day 1-5, every two weeks, based on the recommended dose from Phase I;

Interventions

Cetuximab

Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks;

Intervention Type: DRUG

Trifluridine/Tipiracil

Phase I:

1. 6 patients (male and female) will be enrolled to evaluate safety. Patients will receive Trifluridine/Tipiracil at a dose of 35mg/m2 (maximum single dose of 80 mg). Patients will be followed up for Dose-Limiting Toxicities (DLTs) (2 Cycles, Day 1-Day 28). If ≤2 patients experience DLTs (2 Cycles, Day 1-Day 28), the study will proceed to Phase II with a dose of 35mg/m2. If ≥3 patients experience DLTs (2 Cycles, Day 1-Day 28), the study will proceed to Phase II with a dose of 30mg/m2.

2. Based on the results of the 35mg/m2 dose group, 6 patients (male and female) will be enrolled in the 30mg/m2 dose group to evaluate safety. Patients will be followed up for DLTs (2 Cycles, Day 1-Day 28). If ≤2 patients experience DLTs (1 Cycle, Day 1-Day 28), the study will proceed with a dose of 30mg/m2 in Phase II.

Phase II:

Trifluridine/Tipiracil: po, twice daily from Day 1-5, every two weeks, based on the recommended dose from Phase I;

Intervention Type: DRUG

Other Intervention Names

Erbitux; TAS-102; FTP/TPI

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wangxia LV

OTHER

Sponsor Role: lead

Responsible Party

Wangxia LV

Deputy Director of Colorectal Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Lv

Role: PRINCIPAL_INVESTIGATOR

Zhejiang Cancer Hospital

Locations

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wangxia Lv

Role: CONTACT

lvwangxia@163.com

+86-13757141026

Facility Contacts

Wangxia Lv

Role: primary

lvwangxia@163.com

+86-13757141026

Other Identifiers

IRB-2023-1072

Identifier Type: -

Identifier Source: org_study_id