A Study of Efficacy and Safety of Fruquintinib (HMPL-013) in Participants With Metastatic Colorectal Cancer (FRESCO-2)

• ClinicalTrials.gov Identifier: NCT04322539
• Recruitment Status: Active, not recruiting
• First Posted: March 26, 2020
• Results First Posted: September 14, 2023
• Last Update Posted: September 14, 2023
• Sponsor: Hutchison Medipharma Limited
• Information provided by (Responsible Party): Hutchmed ( Hutchison Medipharma Limited )

Study Description

Brief Summary:

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib plus best supportive care (BSC) versus placebo plus BSC in participants with refractory metastatic colorectal cancer (mCRC). 691 participants were randomized to one of the following treatment arms in a 2:1 ratio, fruquintinib plus BSC or placebo plus BSC.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer; Metastatic Colon Cancer	Drug: Fruquintinib; Drug: Placebo	Phase 3

Detailed Description:

This is a global, randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial to compare the efficacy and safety of fruquintinib in combination with BSC versus placebo in combination with BSC in metastatic colorectal cancer participants who have progressed on, or were intolerant to, chemotherapy, anti-VEGF and anti-EGFR biologics, and TAS-102 or regorafenib. Participants with MSI-H/MMR deficient tumors must have also received an immune checkpoint inhibitor if approved and available and if deemed appropriate. Subjects with BRAF-mutant tumors must have been treated with a BRAF inhibitor if approved and available and if deemed appropriate.

Metastatic colorectal cancer cannot be cured by surgery. Therefore, treatment principals are primarily aimed at controlling disease progression and prolonging survival. Standard first- and second-line therapy includes cytotoxic drugs such as 5-fluorouracil, oxaliplatin, and irinotecan; anti-VEGF therapy; and, if RAS wild type, anti-EGFR therapy. After the first two lines of chemotherapy, standard third-line treatment is either TAS-102 or regorafenib. There are currently no effective treatments for patients who have progressed on standard, approved therapies, and treatment options include reuse of prior therapies, clinical trials or BSC. Consequently, there is an unmet medical need for additional safe and effective treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 691 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Global Multicenter Randomized Placebo-Controlled Phase 3 Trial To Compare The Efficacy And Safety Of Fruquintinib Plus Best Supportive Care To Placebo Plus Best Supportive Care In Patients With Refractory Metastatic Colorectal Cancer
• Actual Study Start Date: August 12, 2020
• Actual Primary Completion Date: July 29, 2022
• Estimated Study Completion Date: March 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fruquintinib Plus Best Supportive Care (BSC) Group; Participants will be orally administered Fruquintinib 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).	Drug: Fruquintinib; Oral VEGFR inhibitor; Other Name: HMPL-013
Placebo Comparator: Placebo Plus BSC Group; Participants will be orally administered Placebo 5 mg in combination with BSC once daily for 3 weeks of continuous dosing followed by a 1-week break (with each cycle length of 28 days).	Drug: Placebo; Placebo capsule

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From date of randomization to death from any cause (up to 22 months) ]
   OS was defined as the time (months) from date of randomization to death from any cause. OS was calculated as (date of death or last known alive - date of randomization + 1)/30.4375. Participants without report of death at the time of analysis will be censored at the date last known alive.

Secondary Outcome Measures :

1. Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 [ Time Frame: From randomization until the first documentation of objective progression or death, whichever comes first (up to 22 months) ]
   PFS was defined as the time (months) from randomization until the first radiographic documentation of objective progression as assessed by investigator using RECIST v1.1, or death from any cause, whichever comes first. More specifically, PFS was determined using all data until the last evaluable visit prior to or on the date of: (i) radiographic disease progression (PD) per RECIST v1.1; (ii) withdrawal of consent to obtain additional scans on study; or (iii) initiation of subsequent anticancer therapy other than the study drugs, whichever was earlier. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.
2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: From randomization until the first documentation of best overall response (up to 22 months) ]
   ORR was defined as the percentage of participants who achieved a best overall response of confirmed complete response (CR) or partial response (PR), per RECIST v1.1, as determined by the investigator. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm).
3. Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: From randomization until the first documentation of best overall response (up to 22 months) ]
   DCR was defined as percentage of participants achieving a best overall response of confirmed CR, PR, or stable disease (SD) (for at least 7 weeks) per RECIST v1.1, as determined by the investigator. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline.
4. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: From first occurrence of PR or CR until the first documentation progression or death, whichever comes first (up to 22 months ]
   DOR was defined as the time (in months) from the first occurrence of PR or CR by RECIST Version 1.1, until the first date that progressive disease is documented by RECIST Version 1.1, or death, whichever comes first. Only those participants with confirmed responses of CR or PR were included in this analysis. DOR was calculated as (date of death or PD or last assessment - date of first occurrence of confirmed CR or PR + 1)/30.4375.
5. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From start of study drug administration up to 22 months ]
   An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE was considered a TEAE if the onset date was on or after the start of study treatment or if the onset date was missing, or if the AE had an onset date before the start of study treatment but worsened in severity after the study treatment until 37 days after the last dose of study treatment or a new treatment of anti-tumor therapy, whichever was earlier. After this period, treatment-related SAEs were also considered as TEAEs. AEs with an unknown/not reported onset date were also included.
6. Observed Plasma Concentrations of Fruquintinib and Metabolite M11 [ Time Frame: Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 (Day 21): Predose and 2 hours, Cycle 3 (Day 1): Pre-dose, Cycle 3 (Day 21): Pre-dose and 2 hours, Cycle 5, 7, 9, 11, 13, 15 and 17 (Day 1): Pre-dose (Each cycle = 28 days) ]
   Plasma samples were collected from the participants at the defined time points. Plasma concentrations were measured using a validated, specific, and sensitive liquid chromatography tandem mass spectrometry method. M11 is the active metabolite for the study drug.
7. Change From Baseline of Electrocardiogram (ECG) Results - QTcF Intervals Using Fridericia's Formula [ Time Frame: Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) ]
   QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 milliseconds (msec). QTc: QT interval corrected based on the patient's heart rate. QTcF: An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula. QTc = QT/∛(RR) RR = Respiration rate.
8. Change From Baseline of ECG Results -QTcB Intervals Using Bazzett's Formula [ Time Frame: Baseline, Cycle 1 (Day 1 and 21): Pre-dose, 1, 2, 3 and 4 hours; Cycle 2 and 3 (Day 21): Pre-dose (Each cycle = 28 days) ]
   QT Interval: Ventricular depolarization plus ventricular repolarization Normal Range: 400 to 460 msec. QTc: QT interval corrected based on the patient's heart rate. QTcB: An electrocardiographic finding in which the QT interval corrected for heart rate using Bazzett's formula.
9. Correlation Between Fruquintinib Exposure-response With Efficacy (OS) and Safety (AEs) Endpoints [ Time Frame: Up to 42 months ]
   As pre-specified in Exposure-Response final analysis report, fruquintinib exposures response with efficacy and safety endpoints were performed along with data from other clinical studies and the integrated analyses were to be reported separately. Data is not reported for this outcome measure as its analysis is still ongoing and will be reported after study completion.
10. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life Scale Score [ Time Frame: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days) ]
    EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/QOL scale. EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are standardized and converted into scale scores ranging from 0 to 100. For global health status/QOL scale, higher scores represent better QOL. A negative change from baseline value indicates patient condition became worst. Change from baseline in the EORTC QLQ-C30 Global Health Status/Quality of Life Scale scores was performed by visit (i.e., cycle), using a restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach.
11. Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score [ Time Frame: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days) ]
    The EQ-5D-5L is a self-reported health status questionnaire that consisted of six questions used to calculate a health utility score. There were two components to the EQ-5D-5L: a five-item health state profile that assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score and a general VAS score for health status. EQ-5D VAS was used to record participant's rating for his/her current health-related quality of life state on a vertical VAS with scores ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state. The higher the score the better the health status. A negative change from baseline value represents patient condition became worse. Change from baseline in the EQ-5D-5L VAS scores was performed by visit (i.e. cycle), using a REML-based MMRM approach.
12. Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Health Utility Index Scores [ Time Frame: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days) ]
    EQ-5D-5L consisted of 2 components: health state profile and optional VAS. EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problem, 2= slight problem, 3= moderate problem, 4= severe problem, and 5= extreme problem. The response levels collected from the EQ-5D-5L five dimensions as a health profile are converted into an EQ-5D-5L index (utility) scores to represent participants' utility value. The range of health utility index score is from -0.285 to 1, where higher value indicates perfect health and a negative value represents a state worse than dead. Change from baseline in EQ-5D-5L health utility index scores was performed by visit (i.e., cycle), using a REML-based MMRM approach.
13. Health Care Resource Utilization: Duration of Hospital Visits by Participants [ Time Frame: From start of study drug administration up to 22 months ]
    Duration of hospital visit was calculated as = stop date - start date + 1. Mean and standard deviation data for duration of hospital visits (in days) by participants was reported in this outcome measure.
14. Health Care Resource Utilization: Number of Participants With Any Concomitant Medications Prescribed [ Time Frame: From start of study drug administration up to 22 months ]
    Number of participants with any concomitant medications prescribed were reported.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Provide written informed consent;
• Age ≥18 years;
• Histologically and/or cytologically documented metastatic colorectal adenocarcinoma. RAS, BRAF, and microsatellite instability microsatellite instability (MSI)/mismatch repair (MMR) status for each patient must be documented, according to country level guidelines;
• Participants must have progressed on or been intolerant to treatment with either trifluridine/tipiracil (TAS-102) or regorafenib. Participants are considered intolerant to TAS-102 or regorafenib if they have received at least 1 dose of either agents and were discontinued from therapy for reasons other than disease progression. Participants who have been treated with both TAS-102 and regorafenib are permitted. Participants must also have been previously treated with standard approved therapies: fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and, if RAS wild-type, an anti-EGFR therapy;
• Participants with microsatellite-high (MSI-H) or mismatch repair deficient (dMMR) tumors must have been treated with immune checkpoint inhibitors if approved and available in the participant's country unless the patient is ineligible for treatment with a checkpoint inhibitor;
• Participants who received oxaliplatin in the adjuvant setting and developed metastatic disease during or within 6 months of completing adjuvant therapy are considered eligible without receiving oxaliplatin in the metastatic setting. Participants who developed metastatic disease more than 6 months after completion of oxaliplatin-containing adjuvant treatment must be treated with oxaliplatin-based therapy in the metastatic setting to be eligible;
• Body weight ≥40kg;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Have measurable disease according to RECIST Version 1.1, assessed locally. Tumors that were treated with radiotherapy are not measurable per RECIST Version 1.1, unless there has been documented progression of those lesions;
• Expected survival >12 weeks.
• For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form(s) of contraception, that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include: oral hormonal contraception (combined estrogen/ progestogen, or progestogen-only) associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal ligation, vasectomized partner, or true sexual abstinence in line with the preferred and usual lifestyle of the participant. Highly effective contraception should always be combined with an additional barrier method (eg, diaphragm, with spermicide). The same criteria are applicable to male participants involved in this clinical trial if they have a partner of childbirth potential, and male participants must always use a condom.
• Participants with BRAF-mutant tumors must have been treated with a BRAF inhibitor if approved and available in the participant's home country unless the patient is ineligible for treatment with a BRAF inhibitor.

Exclusion Criteria:

• Absolute neutrophil count (ANC) <1.5×109/L, platelet count <100×109/L, or hemoglobin <9.0 g/dL. Blood transfusion within 1 week prior to enrollment for the purpose of increasing the likelihood of eligibility is not allowed;
• Serum total bilirubin >1.5 × the upper limit of normal (ULN). Participants with Gilbert syndrome, bilirubin <2 X ULN, and normal AST/ALT are eligible;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × ULN in participants without hepatic metastases; ALT or AST >5 × ULN in participants with hepatic metastases;
• Serum creatinine >1.5 × ULN or creatinine clearance <60 mL/min. Creatinine clearance can either be measured in a 24-hour urine collection or estimated by the Cockroft-Gault equation.
• Urine dipstick protein ≥2+ or 24-hour urine protein ≥1.0 g/24-h. Participants with greater than 2+ proteinuria by dipstick must undergo a 24-hour urine collection to assess urine protein level;
• Uncontrolled hypertension, defined as: systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg despite optimal medical management. Participants were required to have blood pressure values below both limits. Repeated assessments were permitted;
• International Normalized Ratio (INR) >1.5 x ULN or activated partial thromboplastin time (aPTT) >1.5 × ULN, unless the patient is currently receiving or intended to receive anticoagulants for prophylactic purposes;
• History of, or active gastric/duodenal ulcer or ulcerative colitis, active hemorrhage of an unresected gastrointestinal tumor, history of perforation or fistulas; or any other condition that could, in the investigator's judgment, result in gastrointestinal hemorrhage or perforation; within the 6 months prior to screening;
• History or presence of hemorrhage from any other site (eg, hemoptysis or hematemesis) within 2 months prior to screening;
• History of a thromboembolic event, including deep vein thrombosis (DVT), pulmonary embolism (PE), or arterial embolism within 6 months prior to screening.
• Stroke and/or transient ischemic attack within 12 months prior to screening;
• Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction or coronary artery bypass surgery within 6 months prior to enrollment, severe or unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, ventricular arrhythmias requiring treatment, or left ventricular ejection fraction (LVEF) <50% by echocardiogram;
• Mean corrected QT interval using the Fridericia method (QTcF) >480 msec or any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in a first-degree relative.
• Concomitant medications with a known risk of causing QT prolongation and/or Torsades de Pointes.
• Systemic anti-neoplastic therapies (except for those described in Exclusion 18) or any investigational therapy within 4 weeks prior to the first dose of study drug, including chemotherapy, radical radiotherapy, hormonotherapy, biotherapy and immunotherapy;
• Systemic small molecule targeted therapies (eg, tyrosine kinase inhibitors) within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
• Palliative radiotherapy for bone metastasis/lesion within 2 weeks prior to the initiation of study drug;
• Brachytherapy (i.e., implantation of radioactive seeds) within 60 days prior to the first dose of study drug.
• Use of strong inducers or inhibitors of CYP3A4 within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug;
• Surgery or invasive procedure (i.e., a procedure that includes a biopsy; central venous catheter placement is allowed) within 60 days prior to the first dose of study drug or unhealed surgical incision;
• Any unresolved toxicities from a previous antitumor treatment greater than CTCAE v5.0 Grade 1 (except for alopecia or neurotoxicity grade≤2);
• Known human immunodeficiency virus (HIV) infection;
• Known history of active viral hepatitis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Participants with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load.
• Clinically uncontrolled active infection requiring IV antibiotics;
• Tumor invasion of a large vascular structure, eg, pulmonary artery, superior or inferior vena cava;
• Women who are pregnant or lactating;
• Brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease for 14 days or longer; participants requiring steroids within 4 weeks prior to start of study treatment are excluded;
• Other malignancy, except for non-melanoma skin cancer, in situ cervical ca or bladder ca (Tis and T1) that have been adequately treated during the 5 years prior to screening;
• Inability to take medication orally, dysphagia or an active gastric ulcer resulting from previous surgery (eg, gastric bypass) or a severe gastrointestinal disease, or any other condition that investigators believe may affect absorption of the investigational product;
• Other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other condition (e.g., current alcohol or drug abuse) that investigators suspect may prohibit use of the investigational product, affect interpretation of study results, or put the patient at undue risk of harm based on the investigator's assessment;
• Known hypersensitivity to fruquintinib (or placebo) or any of its inactive ingredients including the azo dyes Tartrazine - FD&C Yellow 5 and Sunset yellow FCF - FD&C Yellow 6;
• Participants who have received prior fruquintinib;
• Live vaccine <28days before the first dose of study drug(s). Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Arizona

Phoenix, Arizona, United States, 85054

Arizona Oncology Associates, PC-HOPE

Tucson, Arizona, United States, 85704

United States, California

California Research Institute (CRI)

Los Angeles, California, United States, 90027

City of Hope Comprehensive Cancer Center

Los Angeles, California, United States, 91010

United States, Colorado

Rocky Mountain Cancer Center

Aurora, Colorado, United States, 80012

United States, District of Columbia

The George Washington University Medical Center

Washington, District of Columbia, United States, 20052

United States, Florida

Sarah Cannon Research Institute-S-Ft. Myers (FCS South)

Fort Myers, Florida, United States, 33901

Mayo Clinic Florida

Jacksonville, Florida, United States, 32224

Mount Sinai Medical Center

Miami Beach, Florida, United States, 33140

Cancer Care Centers of Brevard, Inc.

Palm Bay, Florida, United States, 32901

Sarah Cannon Research Institute-N-St Pete (FCS North)

Saint Petersburg, Florida, United States, 33705

Sarah Cannon Research Institute-Pan-Tallahassee (FCS Panhandle)

Tallahassee, Florida, United States, 32308

Sarah Cannon Research-E-WPB (Florida Cancer Specialists-FCS East)

West Palm Beach, Florida, United States, 33401

United States, Georgia

Emory Winship Cancer Institute

Atlanta, Georgia, United States, 30322

United States, Illinois

Illinois Cancer Specialists

Arlington Heights, Illinois, United States, 60005

Affiliated Oncologists

Chicago Ridge, Illinois, United States, 60415

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Kansas

XCancer / Central Care Cancer Center

Garden City, Kansas, United States, 67846

United States, Kentucky

University of Louisville - James Brown Cancer Center

Louisville, Kentucky, United States, 40202

Norton Cancer Institute Audubon

Louisville, Kentucky, United States, 40217

United States, Louisiana

Hematology Oncology Clinic

Baton Rouge, Louisiana, United States, 70809

XCancer / Pontchartrain Cancer Center

Hammond, Louisiana, United States, 70403

United States, Maryland

Maryland Oncology Hematology, P.A.

Columbia, Maryland, United States, 21044

United States, Michigan

University of Michigan Health System

Ann Arbor, Michigan, United States, 48109

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Minnesota

Minnesota Oncology

Minneapolis, Minnesota, United States, 55404

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55905

United States, Missouri

Center for Pharmaceutical Research

Kansas City, Missouri, United States, 64114

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

United States, New Jersey

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States, 08901

United States, New Mexico

XCancer / New Mexico Oncology & Hematology Consultants

Albuquerque, New Mexico, United States, 87109

United States, South Carolina

Charleston Oncology

Charleston, South Carolina, United States, 29414

United States, Tennessee

Sarah Cannon Tennessee Oncology

Nashville, Tennessee, United States, 37203

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

Texas Oncology - Austin

Austin, Texas, United States, 78705

Texas Oncology Baylor Sammons

Dallas, Texas, United States, 75246

Texas Oncology-El Paso

El Paso, Texas, United States, 79902

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Texas Oncology-McAllen

McAllen, Texas, United States, 78503

Texas Oncology-San Antonio

San Antonio, Texas, United States, 78217

Texas Oncology-Tyler

Tyler, Texas, United States, 75702

United States, Virginia

Virginia Oncology Associates

Norfolk, Virginia, United States, 23502

United States, Washington

Providence Regional Cancer Partnership

Everett, Washington, United States, 98201

Northwest Cancer Specialists, P.C.

Vancouver, Washington, United States, 98684

United States, Wisconsin

Medical College of Wisconsin/ Froedtert Hospital

Milwaukee, Wisconsin, United States, 53226

Australia, Queensland

Integrated Clinical Oncology Network Pty Ltd (Icon)

Brisbane, Queensland, Australia, 4001

Australia, South Australia

The Queen Elizabeth Hospital

Adelaide, South Australia, Australia, 5011

Flinders Medical Centre

Adelaide, South Australia, Australia, 5042

Australia, Victoria

Western Health

Melbourne, Victoria, Australia, 3021

Austin Hopistal Medical Oncology Unit

Melbourne, Victoria, Australia, 3084

Monash Health

Melbourne, Victoria, Australia, 3168

Austria

Ordensklinikum Linz Barmherzige Schwestern

Linz, AUT, Austria, 4010

Schwerpunktkrankenhaus Feldkirch

Rankweil, AUT, Austria, 6830

Klinikum Steyr

Steyr, AUT, Austria, 4400

Klinikum Wels-Grieskirchen GmbH

Wels, AUT, Austria, 4600

Landesklinikum Wiener Neustadt

Wiener Neustadt, AUT, Austria, 2700

Wiener Gesundheitsverbund - Klinik Ottakring

Wien, AUT, Austria, 1160

Belgium

Onze-Lieve-Vrouwziekenhuis OLV - Campus Aalst

Aalst, BEL, Belgium, 9300

UCL St-Luc

Brussels, BEL, Belgium, 1200

Grand Hopital de Charleroi

Charleroi, BEL, Belgium, 6000

UZ Antwerpen

Edegem, BEL, Belgium, 2650

Centres Hospitaliers Jolimont

Haine-Saint-Paul, BEL, Belgium, 7100

UZ Leuven

Leuven, BEL, Belgium, 3000

AZ Delta Roeselare

Roeselare, BEL, Belgium, 8800

AZ Turnhout

Turnhout, BEL, Belgium, 2300

CHU Mont-Godinne

Yvoir, BEL, Belgium, 5530

Clinique CHC MontLegia

Liège, Wallonia, Belgium, 4000

CHU de Lige - Domaine Universitaire du Sart Tilman

Liège, Wallonia, Belgium, 4001

Czechia

Masaryk Memorial Cancer Institute, Hematoonkologie

Brno, Moravia, Czechia, 60200

Fakultni nemocnice Olomouc, Onkologicka klinika

Olomouc, Moravia, Czechia, 77900

Vseobecna Fakultni Nemocnice VFN, Onkologicka Klinika

Prague, Czechia, 12808

Estonia

East Tallinn Central Hospital Centre of Oncology

Tallinn, Harju, Estonia, 11312

Sihtasutus Pohja-Eesti Regionaalhaigla (PERH) (North Estonia Medical Centre)

Tallinn, Harju, Estonia, 13419

Tartu University Hospital Clinic of Haematology and Oncology

Tartu, Estonia, 50406

France

CHU Besancon

Besançon, Franche-Comte, France, 25000

Institut Bergonie

Bordeaux, FRA, France, 33000

Unicancer

Caen, FRA, France, 14000

Centre Georges-Francois Leclerc

Dijon, FRA, France, 21000

ICM-Val d'Aurelle

Montpellier, FRA, France, 34298

Saint-Louis Hospital

Paris, FRA, France, 75010

Hopital St Antoine

Paris, FRA, France, 75012

Hopital Pitie Salptriere

Paris, FRA, France, 75013

CHU Poitiers

Poitiers, FRA, France, 86000

Centre hospitalier Annecy Genevois

Pringy, FRA, France, 74370

Centre Hospitalier Universitaire CHU de Rennes - Hopital de Pontchaillou

Rennes, FRA, France, 35033

Institut de cancerologie Strasbourg-Europe

Strasbourg, FRA, France, 67033

Institut Gustave Roussy

Villejuif, Paris, France, 94805

Germany

Universitaetsklinikum Erlangen

Erlangen, Bavaria, Germany, 91054

HELIOS Klinikum Berlin-Buch Saarow

Berlin, DEU, Germany, 13125

Charite - Universitaetsmedizin Berlin

Berlin, DEU, Germany, 13353

Universitaetsklinik Dresden

Dresden, DEU, Germany, 1307

University Hospital Essen

Essen, DEU, Germany, 45147

Institut fr Klinisch Onkologische ForschungKrankenhaus Nordwest GmbH

Frankfurt Am Main, DEU, Germany, 60488

Haematologisch-Onkologische Praxis Hamburg Eppendorf

Hamburg, DEU, Germany, 20249

Asklepios Tumorzentrum Hamburg AK Altona

Hamburg, DEU, Germany, 22763

Universitaeres Krebszentrum Leipzig

Leipzig, DEU, Germany, 4103

RKH Kliniken

Ludwigsburg, DEU, Germany, 22763

Universitaetsmedizin Mannheim- III. Medizinische Klinik

Mannheim, DEU, Germany, 68167

Klinikum Neuperlach

Muenchen, DEU, Germany, 81737

Zentrum für Hämatologie und Onkologie MVZ GmbH

Porta Westfalica, DEU, Germany, 32457

Hungary

Del-Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet, Szent Laszlo Korhaz

Budapest, HUN, Hungary, 1097

National Institute of Oncology

Budapest, HUN, Hungary, 1122

Magyar Honvedseg Egeszsegugyi Kozpont

Budapest, HUN, Hungary, H-1062

Debreceni Egyetem Klinikai Kozpont

Debrecen, HUN, Hungary, 4032

Bacs- Kiskun Megyei Korhaz

Kecskemét, HUN, Hungary, 6000

Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz

Nyiregyhaza, HUN, Hungary, 4400

Hetenyi G Korhaz, Onkologiai Kozpont

Szolnok, HUN, Hungary, 5004

Szent Borbala Korhaz

Tatabanya, HUN, Hungary, 2800

Somogy Megyei Kaposi Mor Oktato Korhaz, Klinikai Onkologiai Osztaly

Kaposvár, Somogy, Hungary, 7400

Zala Megyei Szent Rafael Korhaz, Onkologiai Osztaly, F epulet 3. em.

Zalaegerszeg, Zala, Hungary, 8900

Bekes Megyei Kozponti Korhaz, Pandy Kalman Tagkorhaz, Megyei Onkologiai Kozpont

Gyula, Hungary, 5700

Italy

Fondazione Poliambulanza Hospital

Brescia, ITA, Italy, 25124

Policlinico San Martino di Genova

Genova, ITA, Italy, 16132

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, ITA, Italy, 20133

ASST Grande Ospedale Metropolitano Niguarda

Milano, ITA, Italy, 20162

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, ITA, Italy, 80131

Istituto Oncologico Veneto Irccs

Padova, ITA, Italy, 35128

Azienda Ospedaliero Universitaria Pisana

Pisa, ITA, Italy, 56126

Azienda USL-IRCCS di Reggio Emilia

Reggio Emilia, ITA, Italy, 42123

AO Card G Panico

Tricase, ITA, Italy, 73039

Ospedale San Bortolo Azienda ULSS8 Berica - Distretto Est

Vicenza, ITA, Italy, 36100

Istituto Clinico Humanitas

Rozzano MI, Lombardy, Italy, 20089

Japan

Aichi Cancer Center

Nagoya, Aichi, Japan, 464-8681

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan, 277-8577

Shikoku Cancer Center

Matsuyama City, Ehime, Japan, 791-0280

Kyushu Cancer Center

Fukuoka-shi, Fukuoka, Japan, 811-1395

Hokkaido University Hospital

Sapporo-shi, Hokkaido, Japan, 060-8648

St. Marianna University School of Medicine Hospital

Kawasaki-shi, Kanagawa, Japan, 216-8511

Kindai University Hospital

Osakasayama-shi, Osaka, Japan, 589-8511

Osaka University Hospital

Suita-shi, Osaka, Japan, 565-0871

Shizuoka Cancer Center

Shizuoka, Sunto-gun, Japan, 411-8777

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan, 104-0045

Poland

M Sklodowska Curie Memorial Cancer Center, Klinika Gastroenterologii Onkologicznej

Warszawa, Masovia, Poland, 02034

Bialostockie Centrum Onkologii im. Marii Skodowskiej-Curie

Bialystok, Podlaskie, Poland, 15-027

Spain

Hospital Universitari Vall dHebron

Barcelona, ESP, Spain, 8035

Hospital Universitario Reina Sofa

Córdoba, ESP, Spain, 14004

Hospital General Universitario de Elche

Elche, ESP, Spain, 3203

Hospital Universitario Ramón y Cajal

Madrid, ESP, Spain, 28034

Hospital Clinico San Carlos

Madrid, ESP, Spain, 28040

Hospital Universitario 12 de Octubre

Madrid, ESP, Spain, 28041

Hospital Universitario La Paz

Madrid, ESP, Spain, 28046

Hospital Universitario HM Sanchinarro

Madrid, ESP, Spain, 28050

Hospital Universitario Puerta de Hierro

Majadahonda, ESP, Spain, 28222

Hospital Regional Universitario Carlos Haya

Malaga, ESP, Spain, 29010

Hospital Universitario Central de Asturias

Oviedo, ESP, Spain, 33013

Hospital Universitario Marques de Valdecilla

Santander, ESP, Spain, 39008

Hospital ClÃ-nico Universitario de Santiago-CHUS

Santiago De Compostela, ESP, Spain, 15706

Hospital General Universitario Gregorio Maranon HGUGM

Madrid, Spain, 28007

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Hospital Clinico Universitario de Valencia

Valencia, Spain, 46010

United Kingdom

Aberdeen Royal Infirmary

Aberdeen, GBR, United Kingdom, AB25 2ZN

The Royal Marsden Hospital

London, GBR, United Kingdom, SW3 6JJ

Sarah Cannon Research Institute UK

London, Middlesex, United Kingdom, W1G 6AD

Sponsors and Collaborators

Hutchison Medipharma Limited

Investigators

• Study Director: William Schelman, MD, PhD; HUTCHMED International Corporation

  Study Documents (Full-Text)

Documents provided by Hutchmed ( Hutchison Medipharma Limited ):

Study Protocol and Statistical Analysis Plan  [PDF] July 21, 2022

More Information

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

Dasari A, Sobrero A, Yao J, Yoshino T, Schelman W, Yang Z, Chien C, Kania M, Tabernero J, Eng C. FRESCO-2: a global Phase III study investigating the efficacy and safety of fruquintinib in metastatic colorectal cancer. Future Oncol. 2021 Aug;17(24):3151-3162. doi: 10.2217/fon-2021-0202. Epub 2021 May 17.

• Responsible Party: Hutchison Medipharma Limited
• ClinicalTrials.gov Identifier: NCT04322539
• Other Study ID Numbers: 2019-013-GLOB1
• First Posted: March 26, 2020
• Results First Posted: September 14, 2023
• Last Update Posted: September 14, 2023
• Last Verified: September 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hutchmed ( Hutchison Medipharma Limited ):

colon; colorectal; mcrc; crc; metastatic colon; metastatic colorectal; VEGF; VEGFR

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