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

NCT ID: NCT02314819

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 416 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-01-17

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

treatment arm

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.

Group Type: ACTIVE_COMPARATOR

fruquintinib

Intervention Type: DRUG

fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off

control arm

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

fruquintinib placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off

Interventions

fruquintinib

fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off

Intervention Type: DRUG

placebo

fruquintinib placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off

Intervention Type: DRUG

Other Intervention Names

HMPL-013; HMPL-013 placebo

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: collaborator

Eighty-One Hospital of People's Liberation Army

OTHER

Sponsor Role: collaborator

Hutchison Medipharma Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jin Li, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Hutchison Medi Pharma Investigational Site

Hefei, Anhui, China

Hutchison Medi pharma Investigational Site

Beijing, Beijing Municipality, China

Hutchison Medi Pharma Investigational Site

Guangzhou, Guangdong, China

Hutchison Medi Pharma investigational site

Shenzhen, Guangdong, China

Hutchison Medi Pharma Investigational Site

Liuzhou, Guangxi, China

Hutchison Medi Pharma Investigational Site

Harbin, Heilongjiang, China

Hutchison Medi Pharma Investigational Site

Changsha, Hunan, China

Hutchison Medi Pharma Investigational Site

Changzhou, Jiangsu, China

Hutchison Medi Pharma Investigational Site

Nanjing, Jiangsu, China

Hutchison Medi Pharma Investigational Site

Nantong, Jiangsu, China

Hutchison Medi Pharma Investigational Site

Xuzhou, Jiangsu, China

Hutchison Medi Pharma Investigational Site

Changchun, Jilin, China

Hutchison Medi Pharma Investigational Site

Qingdao, Shandong, China

Hutchison Medi Pharma Investigational Site

Shanghai, Shanghai Municipality, China

Hutchison Medi Pharma Investigational Site

Hangzhou, Zhejiang, China

Countries

China

References

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.

Reference Type: RESULT

PMID: 29946728 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34408440 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33325251 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32901330 (View on PubMed)

Other Identifiers

2013-013-00CH1

Identifier Type: -

Identifier Source: org_study_id