Study of Fruquintinib in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Fruquintinib administered at 5mg once daily 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 advanced Colorectal Cancer (CRC) in Phase Ib 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 metastatic CRC second line or above standard chemotherapy.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter Phase II clinical trial to compare the efficacy and safety of Fruquintinib plus Best Supportive Care (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: Progression free survival (PFS) (According to RECIST Version 1.1). Secondary Efficacy Endpoints: Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS). Safety and tolerance will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI common terminology criteria for adverse events (CTC AE) Version 4.0.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Trial to Compare the Efficacy and Safety of Fruquintinib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Colorectal Cancer as 3rd or Above Therapy

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 ≥ 40 Kg Histological or cytological confirmed metastatic colorectal cancer Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Failed 2 or more lines of chemotherapy 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 Central nervous system (CNS) metastasis One of the following conditions: 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) Evidence or a history of bleeding tendency within two months of the enrollment, regardless of seriousness History of artery/venous thromboembolic events in 12 months, such as cerebral vascular accident (including transient ischemic attack) etc. History of acute myocardial infarction, acute coronary syndrome or coronary artery bypass graft (CABG) in 6 months 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, once daily (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, once daily (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>* 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 |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS refers to the time interval between the randomization date and the initial record of PD or date of death, whichever is earlier. The presence of PD shall be determined in accordance with the result of the evaluation performed by the investigator, using with RECIST v1.1 criteria. The date of final tumor evaluation will be used as the censoring date for subjects who have not presented with disease progression or death by that date. The date of randomization will be used as the censoring date for subjects which have no death and post-baseline tumor evaluation. If a subject has no post-baseline tumor evaluation but recorded as dead, death will be count as PFS event. | From randomization until the date of first documented progression or date of death from any cause, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The ORR is defined as the rate of complete response (CR) or partial response (PR) as the best overall response (BOR), based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined by RECIST v1.1, for the ITT set of response evaluable subjects. Subjects who have no post-baseline tumor evaluation shall be regarded as subjects without ORR. Subjects who qualify for evaluation of CR or PR should have at least one available lesion for measurement with RECIST v1.1. | From randomization up to progressive disease or end of treatment (EOT) due to any cause. | 
| Disease Control Rate (DCR) | The DCR is defined as the rate of corroborant CR, PR and stable disease (SD) as the BOR, based on evaluation of target lesions and non-target lesions with corroborant radiological method and determined according to RECIST v1.1, for the ITT set of response evaluable subjects. | From randomization up to progressive disease or EOT due to any cause. | 
| Over Survival (OS) | The OS refers to the time interval between the randomization date and the date of death (any cause). The final known date of survival will be used as the censoring date for subjects that have not been reported to have died by the time of analysis. | From randomization until death due to any cause. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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013, Colorectal cancer, Fruquintinib