Safety of Cetuximab and Trifluridin Tipiracil as the Third-line Therapy in the RASwt mCRC

Safety of Cetuximab in Combination With Trifluridin Tipiracil in the Third-line Treatment of RASwt Metastatic Colorectal Cancer

This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms Malignant
• Intervention / Treatment: Drug: Cetuximab + trifluridin tipiracil

Detailed Description

This was a single-arm, prospective study to investigate the safety of cetuximab in combination with trifluridin tipiracil (TAS-102) in the third-line treatment of Chinese patients with RAS wild-type mCRC. Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; after 1 cycle will be observed, and if ≤ 2 patients experience DLT, this dose level will be the recommended phase II dose; if ≥ 3 patients experience DLT, additional 6 patients will receive dose level 0. ( Dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;) If ≤ 2 individuals experience DLT, this dose level is the recommended Phase II dose; if ≥ 3 individuals experience DLT, the study will be stopped.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Jieying Zhang; Phone Number: +8613554281983; Email: whxhzjy@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-75 years old male or female;
• Histologically or cytologically confirmed metastatic colon or rectal adenocarcinoma; excluding appendiceal cancer and anal canal cancer;
• Previously received second-line treatment, at least 2 standard chemotherapy regimens(including fluorouracil, capecitabine, irinotecan, oxaliplatin, raltitrexed and anti-VEGF, anti-EGFR, etc.), if already accepted anti-EGFR treatment achieved at least PR or above;
• ECOG PS 0-1;
• At least one measurable lesion by CT or MRI (according to RECIST 1.1 criteria, the longest diameter of tumor lesion CT/MRI scan ≥ 10 mm, lymph node lesion CT/MRI scan shortest diameter ≥ 15 mm);
• RAS gene mutation detection results are wild-type. The test sample can be the primary tumor or metastasis sample;
• Can receive oral drug treatment;

• Normal function of major organs, meeting the following criteria within 14 days before the start of treatment:

  1. neutrophil count ≥ 1.5 × 10*9/L;
  2. Platelet count ≥ 75 × 10*9/L;
  3. Hemoglobin ≥ 9.0 g/dL;
  4. AST ≤ 2.5 × UNL (upper limit of normal) (if liver metastasis AST ≤ 5 × UNL);
  5. ALT ≤ 2.5 × UNL (if liver metastasis AST ≤ 5 × UNL);

  g.Creatinine clearance (calculated according to Cockcroft and Gault formula) > 60 mL/min or serum creatinine ≤ 1.5 × UNL;

• Expected survival time > 3 months (90 days);
• Women of childbearing potential must have used reliable contraception and had a negative pregnancy test within 7 days prior to enrollment and be willing to use an appropriate method of contraception during the trial and for 6 months after the last dose of trial drug. Males must agree to use an adequate method of contraception or have been surgically sterilized during the trial and for 6 months after the last dose of trial drug;
• The patients voluntarily participated in this study and signed the informed consent form, with good compliance and cooperation in the follow-up.

Exclusion Criteria:

• Previously treated with regorafenib, fruquintinib, TAS-102;
• Participated in another drug clinical trial in the past 4 weeks, or received systemic chemotherapy, radiotherapy or biological therapy in the past 4 weeks;
• Known brain metastases or strongly suspected brain metastases;
• Patients with known BARF mutations should be excluded;
• Synchronous cancer or metachronous cancer with disease-free survival ≥ 5 years (except colorectal cancer), excluding mucosal cancer (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.) that has been cured or may be cured by local resection;
• Factors that significantly affect the absorption of oral drugs, such as inability to swallow, chronic diarrhea and gastric intestinal obstruction; ucontrolled Crohn's disease or ulcerative colitis;
• Serosal effusion (including pleural effusion, ascites, pericardial effusion) with clinical symptoms and requiring symptomatic treatment;
• Pregnant or lactating women; patients of childbearing potential are unwilling or unable to take effective contraceptive measures;
• Known to be allergic to the study drug, study drug class and its ingredients;
• Conditions requiring systemic steroid treatment (except topical steroid and cetuximab pretreatment);
• History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
• Active local or systemic infection requiring treatment;
• Cardiac function classification (NYHA classification) ≥ Grade III or severe heart disease;
• Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or active hepatitis B, C;
• Toxicity not recovered (CTCAE > grade 1) or not completely recovered from previous anticancer surgery;
• Patients judged by the Investigator as unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cetuximab and trifluridin tipiracil; Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks;	Drug: Cetuximab + trifluridin tipiracil; Cetuximab will be administered at a fixed dose of 500 mg/m2 once every 2 weeks; trifluridin tipiracil will be administered in a dose de-escalation design: dose level 1: 35 mg/m2 twice daily on days 1-5 once every 2 weeks; Or dose level 0: 30 mg/m2, twice daily, Days 1-5, once every 2 weeks; Other Names: Erbitux；TAS102;TAS-102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT（Dose-limited toxicity）	Determination of RP2D based on incidence of DLT	From Baseline to primary completion date, about 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Eevents	Participants With Incidence of Adverse Eevents During Treatment Period	From Baseline to primary completion date, about 18 months

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Hongli Liu, Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2022
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (ACTUAL): December 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: CT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No