A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients （FRESCO)

Study Overview
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Brief Summary
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Fruquintinib administered at 5mg once daily(QD) in 4 weeks treatment cycle (three weeks on and one week off) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with metastatic colorectal cancer (CRC) in phase Ib and phase 2 study. This study is aimed to evaluate the efficacy and safety of Fruquintinib in the treatment of patients with metastatic CRC who have progressed after second line or above standard chemotherapy

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial to compare the efficacy and safety of Fruquintinib plus BSC versus placebo plus BSC in patients with metastatic colorectal cancer who have progressed after second-line or above standard chemotherapy. After checking eligibility criteria, subjects will be randomized into Fruquintinib plus BSC group (treatment group) or placebo plus BSC group (control group) in a ration of 2:1. Primary Efficacy Endpoint: Overall Survival (OS). Secondary Efficacy Endpoints: Progression free survival (PFS) (According to RECIST Version 1.1), Objective Response Rate (ORR), Disease Control Rate (DCR), . Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.

Official Title
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A Randomized, Double-blind and Placebo-controlled Phase III Trial Comparing Fruquintinib Efficacy and Safety vs Best Support Care (BSC) in Advanced Colorectal Cancer Patients Who Have Failed at Least Second Lines of Chemotherapies

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: fruquintinib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 and ≤ 75 years of age , with ≥ 40Kg Histological or cytological confirmed colorectal cancer ECOG performance status of 0-1 Standard regimen failed or no standard regimen available Adequate hepatic, renal, heart, and hematologic functions At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan) Signed and dated informed consent 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 Evidence of CNS metastasis Intercurrence with one of the following: non-controlled hypertension, coronary artery disease, arrhythmia and heart failure Abuse of alcohol or drugs Less than 4 weeks from the last clinical trial - Previous treatment with VEGFR inhibition Disability of serious uncontrolled intercurrence infection Proteinuria ≥ 2+ (1.0g/24hr) Have evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack) etc. Within 6 months before the first treatment occurs acute myocardial infarction, acute coronary syndrome or CABG Bone fracture or wounds that was not cured for a long time Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: treatment arm<br>treatment arm- subjects will receive Fruquintinib 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. | Drug: fruquintinib<br>* fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off<br>* Other names: HMPL-013;|
| Placebo Comparator: control arm<br>control arm- subjects will receive Fruquintinib placebo 5mg orally, QD, plus BSC for 3 wks on/ 1 wk off. Patients will receive a cycles of 4 weeks of study treatment (1 cycle of study treatment includes 3 weeks of treatment and 1 week of drug discontinuation) or until the occurrence of progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or other conditions that meet the end of treatment criteria. | Drug: placebo<br>* fruquintinib placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off<br>* Other names: HMPL-013 placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | every two months after end of treatment (EOT) observation period at 30 days after the last medication | from randomization until death due to any cause, assessed up to 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | Tumor assessment will be performed using radiography method every 8 weeks, until the occurrence of progressive disease (PD), using RECIST v 1.1 | from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year | 
| Objective Response Rate (ORR) | Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1 | from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year | 
| Disease Control Rate (DCR) | Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1 | from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year | 
| Safety and tolerance evaluated by incidence, severity and outcomes of AEs | Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 4.0. | from first dose to within 30 days after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer