Clinical trial NCT02314819: A Phase III Trial Evaluating Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients （FRESCO)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: colorectal cancer
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
Collaborators: name: Fudan University
name: Eighty-One Hospital of People's Liberation Army
First posted: 2014-12-11
Enrollment: 416
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: overall survival
timeFrame: from randomization until death due to any cause, assessed up to 2 year
Secondary outcomes:
measure: progression free survival
timeFrame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
measure: Objective Response Rate (ORR)
timeFrame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
measure: Disease Control Rate (DCR)
timeFrame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year
measure: Safety and tolerance evaluated by incidence, severity and outcomes of AEs
timeFrame: from first dose to within 30 days after the last dose
Other outcomes:
Locations:
city: Hefei
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Anhui
city: Beijing
country: China
facility: Hutchison Medi pharma Investigational Site
state: Beijing
city: Guangzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Guangdong
city: Shenzhen
country: China
facility: Hutchison Medi Pharma investigational site
state: Guangdong
city: Liuzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Guangxi
city: Harbin
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Heilongjiang
city: Changsha
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Hunan
city: Changzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Jiangsu
city: Nantong
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Jiangsu
city: Xuzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Jiangsu
city: Changchun
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Jilin
city: Qingdao
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Shandong
city: Shanghai
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Shanghai
city: Hangzhou
country: China
facility: Hutchison Medi Pharma Investigational Site
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Jin Li, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018 Jun 26;319(24):2486-2496. doi: 10.1001/jama.2018.7855.
citation: Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Wang N, Zhang B, Zhang Q, Su W, Guo X, Li J. Subgroup Analysis by Liver Metastasis in the FRESCO Trial Comparing Fruquintinib versus Placebo Plus Best Supportive Care in Chinese Patients with Metastatic Colorectal Cancer. Onco Targets Ther. 2021 Aug 11;14:4439-4450. doi: 10.2147/OTT.S307273. eCollection 2021.
citation: Xu R, Qin S, Guo W, Bai Y, Deng Y, Yang L, Chen Z, Zhong H, Pan H, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Xu J, Chen D, Li W, Sun S, Yu Z, Cao P, Li J, Chen H, Wang J, Wang S, Wang H, Wang N, Zhang B, Han R, Su W, Guo X, Li J. Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized, double-blind, Phase III trial. Future Oncol. 2021 Apr;17(11):1339-1350. doi: 10.2217/fon-2020-0875. Epub 2020 Dec 16.
citation: Li J, Guo W, Bai Y, Deng Y, Yang L, Chen Z, Zhong H, Xu R, Pan H, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Xu J, Chen D, Li W, Sun S, Yu Z, Cao P, Shen L, Chen H, Wang S, Wang H, Fan S, Guo X, Wang N, Han R, Zhang B, Qin S. Safety Profile and Adverse Events of Special Interest for Fruquintinib in Chinese Patients with Previously Treated Metastatic Colorectal Cancer: Analysis of the Phase 3 FRESCO Trial. Adv Ther. 2020 Nov;37(11):4585-4598. doi: 10.1007/s12325-020-01477-w. Epub 2020 Sep 8.