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

NCT06379399 | Recruiting Phase 1

• 1 other identifier: IRB-2023-1072
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Keywords

RAS/BRAF wild-type

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-free survival defined as the time elapsed between the randomization and the date of radiologic tumour progression according to RECIST version 1.1 by investigator's judgement or death from any cause, whichever comes first.

  Approximately 12 months

Secondary Outcomes (5)

• Overall survival (OS)

  Approximately 12 months

• Overall Response Rate (ORR)

  Approximately 12 months

• Disease Control Rate( DCR)

  Approximately 12 months

• Quality of life: EORTC QLQ-C30

  Approximately 12 months

• Adverse Events(safety)

  Up to 28 days after discontinuation of study drug or start of subsequent therapy.

Study Arms (1)

Cetuximab Combined With Trifluridine/Tipiracil

EXPERIMENTAL

Drug: Cetuximab; Drug: Trifluridine/Tipiracil

Interventions

Cetuximab DRUG

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

Also known as: Erbitux

Cetuximab Combined With Trifluridine/Tipiracil

Trifluridine/Tipiracil 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;

Also known as: TAS-102, FTP/TPI

Cetuximab Combined With Trifluridine/Tipiracil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection.
• Histologically or cytologically confirmed metastatic adenocarcinoma of the colon; excluding appendiceal and anal canal cancers.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 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).
• Wild-type RAS/BRAF gene detected.
• Able to take oral medication.
• 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;

You may not qualify if:

• Prior treatment with Trifluridine/Tipiracil;
• Patients with known dMMR or MSI-H advanced colorectal cancer who have not previously received anti-PD-1 or PD-L1 inhibitors;
• Participation in another drug clinical trial or receipt of systemic chemotherapy, radiotherapy, or biologic therapy within the past 4 weeks;
• Known or suspected brain metastases;
• 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.);
• Factors significantly affecting oral drug absorption, such as dysphagia, chronic diarrhea, and gastrointestinal obstruction; uncontrolled Crohn's disease or ulcerative colitis;
• Symptomatic malignant effusion requiring symptomatic treatment (including pleural effusion, ascites, pericardial effusion);
• Pregnant or lactating women; patients with reproductive potential unwilling or unable to use effective contraceptive measures;
• Known allergy to the investigational drug, drug class, or its components;
• Requirement for systemic corticosteroid therapy (excluding local steroids and cetuximab pre-treatment);
• History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or radiographic evidence of interstitial lung disease;
• Active local or systemic infections requiring treatment;
• New York Heart Association (NYHA) functional classification ≥II or severe heart disease;
• Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or history of active hepatitis B or hepatitis C;
• Unresolved toxicity (CTCAE\>Grade 1) or incomplete recovery from previous cancer surgery.

Sponsors & Collaborators

• Wangxia LV: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Interventions

Cetuximab; trifluridine tipiracil drug combination

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lv

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wangxia Lv

CONTACT

+86-13757141026; lvwangxia@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director of Colorectal Medicine

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 23, 2024
• Study Start: April 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)