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

Phase 1

Recruiting

• Conditions: Colorectal Neoplasms Malignant
• Interventions: Drug: Cetuximab + trifluridin tipiracil

• Registration Number: NCT05155124
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-12-07
• Study First Submitted QC: 2021-12-07
• Study First Posted: 2021-12-13
• Status Verified: 2022-09
• Study Start: 2022-09
• Last Update Submitted: 2022-09-09
• Last Update Posted: 2022-09-13
• Primary Completion: 2022-10
• Study Completion: 2023-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cetuximab and trifluridin tipiracil	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;

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse Eevents	From Baseline to primary completion date, about 18 months	Participants With Incidence of Adverse Eevents During Treatment Period

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China