Fruquintinib in the Cross-line Treatment of Refractory mCRC

Study Overview
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Brief Summary
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This is a real-world study. Patients with metastatic colorectal cancer who have progressed (PD) after third-line treatment with fruquintinib combined with PD-1 inhibitors will receive fruquintinib combined with TAS-102 as fourth-line therapy. The objective of this study was to observe the efficacy and safety of cross-line（from third to fourth line）treatment with fruquinitinib.

Detailed Description
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This is a real-world study. Patients with metastatic colorectal cancer confirmed by histopathology had previously received 2-line system therapy with fluorouracil, oxaliplatin, irinotecan, anti-VEGF, anti-EGFR (RAS and BRAF wild type) (treatment with anti-VEGF-TKI is not allowed), and had received fruquinitinib combined with PD-1 inhibitors for third-line treatment. After progression (PD) (confirmed by RECIST 1.1 ), fruquinitinib combined with TAS-102 as fourth-line therapy was received. The primary endpoint was observation the overall survival (OS) of fourth-line treatment of mCRC with fruquinitinib and TAS-102. The study objective is to explore the possibility of cross-line rechallenge of fruquinitinib.

Official Title
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A Real-world Study of Fruquintinib in the Cross-line Treatment of Refractory mCRC

Conditions
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Fruquintinib, Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Fruquintinib+PD-1 inhibitors
* Drug: Fruquintinib+TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - To be enrolled in this study, patients must meet all of the following criteria: Age ≥18 years, ≤75 years; No gender limitation; Patients with metastatic colorectal cancer confirmed by histopathology had previously received 2-line system therapy with fluorouracil, oxaliplatin, irinotecan, anti-VEGF, anti-EGFR (RAS and BRAF wild type) (treatment with anti-VEGF-TKI is not allowed), and had received fruquinitinib combined with PD-1 inhibitors for third-line treatment. After progression (PD) (confirmed by RECIST 1.1 ), fruquinitinib combined with TAS-102 as fourth-line therapy was received. Expected survival ≥12 weeks Must have at least one measurable lesion (RECIST1.1). Full organ and bone marrow function. Exclusion Criteria: - Patients will not be admitted to the study if they meet any of the following criteria: Patients with contraindications to study drugs (fruquinitinib, PD-1 inhibitor, TAS-102); allergic to the investigational drug or any of its adjuncts; There are other non-investigational drugs during third-line and fourth-line treatment; Pregnant or lactating female subjects; Patients with a large number of pleural effusion or ascites requiring drainage; Patients considered unsuitable for inclusion in this study by the investigators.

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

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fruquintinib Rechallenge<br>third-line treatment with fruquintinib combined with PD-1 inhibitors fourth-line treatment with fruquintinib combined with TAS-102 | Drug: Fruquintinib+PD-1 inhibitors<br>* Third-line treatment with fruquintinib combined with PD-1 inhibitors. Fruquintinib: 5mg,Oral once daily,2 weeks on/1 week off,Q3W； PD-1 inhibitor：for example, Sintilimab,iv,200mg, Q3W.<br>Drug: Fruquintinib+TAS-102<br>* Fourth-line treatment with fruquintinib combined with TAS-102 . Fruquintinib: 3-5mg(Depending on the patient's physical condition), Oral once daily,3 weeks on/1 week off,Q4W； TAS-102:orally, 35mg/m2 twice daily (maximum dose 80mg in a single dose) for days 1-5, repeated every 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival 2(OS2) | Overall survival (OS) of fourth-line treatment of mCRC with fruquinitinib and TAS-102 | From the date of first fruquinitinib combined with TAS-102 treatment until the date of first documented date of death from any cause , assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate 2(ORR2, investigator based on RECIST1.1) | Objective response rate (ORR) of fourth-line treatment of mCRC with fruquinitinib and TAS-102 | from received fruquinitinib combined with TAS-102 to one year | 
| Progression-free survival 2(PFS2, investigators based on RECIST1.1) | Progression-free survival (PFS) of fourth-line treatment of mCRC with fruquinitinib and TAS-102 | From the date of first fruquinitinib combined with TAS-102 treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 
| Disease control rate 2 (DCR2, investigators based on RECIST1.1) | Disease control rate (DCR) of fourth-line treatment of mCRC with fruquinitinib and TAS-102 | from received fruquinitinib combined with TAS-102 to one year |