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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Colorectal Neoplasms Malignant

Intervention / Treatment
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* Drug: Cetuximab + trifluridin tipiracil


Participation Criteria
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Eligibility Criteria
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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: neutrophil count ≥ 1.5 × 10*9/L; Platelet count ≥ 75 × 10*9/L; Hemoglobin ≥ 9.0 g/dL; AST ≤ 2.5 × UNL (upper limit of normal) (if liver metastasis AST ≤ 5 × UNL); 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cetuximab and trifluridin tipiracil<br>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<br>* 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;<br>* Other names: Erbitux；TAS102;TAS-102;|

What is the study measuring?
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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 |