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

• ClinicalTrials.gov Identifier: NCT02314819
• Recruitment Status: Completed
• First Posted: December 11, 2014
• Last Update Posted: February 17, 2020
• Sponsor: Hutchison Medipharma Limited
• Collaborators: Fudan University; Eighty-One Hospital of People's Liberation Army
• Information provided by (Responsible Party): Hutchmed ( Hutchison Medipharma Limited )

Study Description

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

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer	Drug: fruquintinib; Drug: placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 416 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2014
• Actual Primary Completion Date: January 2017
• Actual Study Completion Date: January 17, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 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.	Drug: fruquintinib; fruquintinib is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off; Other Name: HMPL-013
Placebo Comparator: 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.	Drug: placebo; fruquintinib placebo is a capsule in the form of 1mg and 5mg, orally, once daily, 3 weeks on/ 1 week off; Other Name: HMPL-013 placebo

Outcome Measures

Primary Outcome Measures :

1. overall survival [ Time Frame: from randomization until death due to any cause, assessed up to 2 year ]
   every two months after end of treatment (EOT) observation period at 30 days after the last medication

Secondary Outcome Measures :

1. progression free survival [ Time Frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year ]
   Tumor assessment will be performed using radiography method every 8 weeks, until the occurrence of progressive disease (PD), using RECIST v 1.1
2. Objective Response Rate (ORR) [ Time Frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year ]
   Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1
3. Disease Control Rate (DCR) [ Time Frame: from randomization up to progressive disease or EOT due to any cause, assessed up to 1 year ]
   Tumor assessment will be performed using radiography method every 8 weeks until the occurrence of progressive disease (PD), using RECIST v 1.1
4. Safety and tolerance evaluated by incidence, severity and outcomes of AEs [ Time Frame: from first dose to within 30 days after the last dose ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

China, Anhui

Hutchison Medi Pharma Investigational Site

Hefei, Anhui, China, 230000

China, Beijing

Hutchison Medi pharma Investigational Site

Beijing, Beijing, China, 100071

China, Guangdong

Hutchison Medi Pharma Investigational Site

Guangzhou, Guangdong, China, 510000

Hutchison Medi Pharma investigational site

Shenzhen, Guangdong, China, 518036

China, Guangxi

Hutchison Medi Pharma Investigational Site

Liuzhou, Guangxi, China, 545005

China, Heilongjiang

Hutchison Medi Pharma Investigational Site

Harbin, Heilongjiang, China, 150081

China, Hunan

Hutchison Medi Pharma Investigational Site

Changsha, Hunan, China, 410013

China, Jiangsu

Hutchison Medi Pharma Investigational Site

Changzhou, Jiangsu, China, 213000

Hutchison Medi Pharma Investigational Site

Nanjing, Jiangsu, China, 210000

Hutchison Medi Pharma Investigational Site

Nantong, Jiangsu, China, 226000

Hutchison Medi Pharma Investigational Site

Xuzhou, Jiangsu, China, 221000

China, Jilin

Hutchison Medi Pharma Investigational Site

Changchun, Jilin, China, 130000

China, Shandong

Hutchison Medi Pharma Investigational Site

Qingdao, Shandong, China, 266000

China, Shanghai

Hutchison Medi Pharma Investigational Site

Shanghai, Shanghai, China, 200032

China, Zhejiang

Hutchison Medi Pharma Investigational Site

Hangzhou, Zhejiang, China, 310000

Sponsors and Collaborators

Hutchison Medipharma Limited

Fudan University

Eighty-One Hospital of People's Liberation Army

Investigators

• Principal Investigator: Jin Li, PhD, MD; Fudan University

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Hutchison Medipharma Limited
• ClinicalTrials.gov Identifier: NCT02314819
• Other Study ID Numbers: 2013-013-00CH1
• First Posted: December 11, 2014
• Last Update Posted: February 17, 2020
• Last Verified: February 2019

Keywords provided by Hutchmed ( Hutchison Medipharma Limited ):

colorectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases