Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

Study Overview
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Brief Summary
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This phase II study aims to explore the efficacy and safety of fruquintinib combined with TAS-102 in the third-line treatment of patients with advanced metastatic colorectal cancer.

Detailed Description
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This is a prospective, single center, one-arm phase II study. A total of 54 advanced mCRC patients refractory to standard therapies will be enrolled and administered with fruquintinib (4mg/d, qd po, D1-21, Q4W) combined with TAS-102 (70mg/m2/d, bid po, D1-5, 8-12, Q4W) until intolerable toxicity, disease progression or death. Primary endpoint of this study is PFS and secondary endpoints are OS, ORR, DCR and safety.

Official Title
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Phase II Study of Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: fruquintinib plus TAS-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 and ≤ 75 years of age; Histological or cytological confirmed advanced metastatic colorectal cancer; Refractory to at least second line standard treatment containing fluorouracil, oxaliplatin and irinotecan; At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan or 20mm by conventional CT scan); ECOG performance status of 0-1; Life expectancy ≥ 12 weeks; No previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor (TKI); Signed and dated informed consent; Adequate hepatic, renal, heart, and hematologic functions; Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. Exclusion Criteria: Pregnant or lactating women; Any factors that influence the usage of oral administration or any disease or condition that affects drug absorption; Previous treatment with TAS-102; Participated in clinical trials of other drugs within four weeks before enrollment; Received other systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy; International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN; Clinically significant electrolyte abnormalities; Subjected with hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg; Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previous anti-cancer treatment; Incomplete healing of skin wound, surgical site, traumatic site, severe mucosal ulcer or fracture; Conditions that may cause gastrointestinal bleeding and perforation determined by the researcher; History of arterial thrombosis or deep venous thrombosis within 6 months before enrollment; Stroke and / or transient cerebral ischemia occurred within 12 months before enrollment; Cardiovascular diseases with significant clinical significance; LVEF<50%; Congestive heart failure New York Heart Association (NYHA) grade > 2; Evidence of CNS metastasis; Previous treatment with VEGFR inhibition; Ventricular arrhythmias requiring drug treatment; Proteinuria ≥ 2+ (1.0g/24hr); Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy; Other malignant tumors in the past 5 years, except skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ; Active infection that is not controlled clinically, such as acute pneumonia, active hepatitis B or hepatitis C; By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the 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: fruquintinib plus TAS-102<br>fruquintinib plus TAS-102, orally given, Q4W | Drug: fruquintinib plus TAS-102<br>* fruquintinib 4mg/d, qd po, D1-21, Q4W; TAS-102 70mg/m2/d, bid po, D1-5, 8-12, Q4W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free Survival | from randomization up to progressive disease or EOT due to any cause, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival | from randomization until death due to any cause, assessed up to 3 years | 
| DCR | Disease Control Rate | from randomization up to progressive disease or EOT due to any cause, up to 2 years | 
| ORR | Objective Response Rate | from randomization up to progressive disease or EOT due to any cause, up to 2 years | 
| Safety and tolerance | Safety and tolerance evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0 | from first dose to within 30 days after the last dose |