AzTrials
AzTrials

Metastatic Colorectal CancerPhase 3FRESCO-2NCT04322539

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

A Phase 3 study testing Fruquintinib in people with Metastatic Colorectal Cancer and Metastatic Colon Cancer, run by Hutchison Medipharma Limited at 153 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fruquintinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
691 participants
Where
153 sitesin 14 countries
Study dates
12 Aug 2020to 24 Apr 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

153 sites in 14 countries.

153 sites in 14 countries

United States45 sites

  • XCancer / New Mexico Oncology & Hematology Consultants

    Albuquerque, New Mexico, 87109

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109

  • Illinois Cancer Specialists

    Arlington Heights, Illinois, 60005

  • Emory Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Rocky Mountain Cancer Center

    Aurora, Colorado, 80012

  • Texas Oncology - Austin

    Austin, Texas, 78705

  • Hematology Oncology Clinic

    Baton Rouge, Louisiana, 70809

  • Charleston Oncology

    Charleston, South Carolina, 29414

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Affiliated Oncologists

    Chicago Ridge, Illinois, 60415

  • Maryland Oncology Hematology, P.A.

    Columbia, Maryland, 21044

  • Texas Oncology Baylor Sammons

    Dallas, Texas, 75246

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Texas Oncology-El Paso

    El Paso, Texas, 79902

  • Providence Regional Cancer Partnership

    Everett, Washington, 98201

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

    Fort Myers, Florida, 33901

  • XCancer / Central Care Cancer Center

    Garden City, Kansas, 67846

  • XCancer / Pontchartrain Cancer Center

    Hammond, Louisiana, 70403

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Center for Pharmaceutical Research

    Kansas City, Missouri, 64114

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • California Research Institute (CRI)

    Los Angeles, California, 90027

  • City of Hope Comprehensive Cancer Center

    Los Angeles, California, 91010

  • University of Louisville - James Brown Cancer Center

    Louisville, Kentucky, 40202

  • Norton Cancer Institute Audubon

    Louisville, Kentucky, 40217

  • Texas Oncology-McAllen

    McAllen, Texas, 78503

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Medical College of Wisconsin/ Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Minnesota Oncology

    Minneapolis, Minnesota, 55404

  • Sarah Cannon Tennessee Oncology

    Nashville, Tennessee, 37203

  • Vanderbilt Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Cancer Care Centers of Brevard, Inc.

    Palm Bay, Florida, 32901

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Texas Oncology-San Antonio

    San Antonio, Texas, 78217

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

    St. Petersburg, Florida, 33705

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

    Tallahassee, Florida, 32308

  • Arizona Oncology Associates, PC-HOPE

    Tucson, Arizona, 85704

  • Texas Oncology-Tyler

    Tyler, Texas, 75702

  • Northwest Cancer Specialists, P.C.

    Vancouver, Washington, 98684

  • The George Washington University Medical Center

    Washington D.C., District of Columbia, 20052

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

    West Palm Beach, Florida, 33401

Other trials in United States

Spain16 sites

  • Hospital Universitari Vall dHebron

    Barcelona, ESP, 8035

  • Hospital Universitario Reina Sofa

    Córdoba, ESP, 14004

  • Hospital General Universitario de Elche

    Elche, ESP, 3203

  • Hospital Universitario Ramón y Cajal

    Madrid, ESP, 28034

  • Hospital Clinico San Carlos

    Madrid, ESP, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, ESP, 28041

  • Hospital Universitario La Paz

    Madrid, ESP, 28046

  • Hospital Universitario HM Sanchinarro

    Madrid, ESP, 28050

  • Hospital General Universitario Gregorio Maranon HGUGM

    Madrid, 28007

  • Hospital Universitario Puerta de Hierro

    Majadahonda, ESP, 28222

  • Hospital Regional Universitario Carlos Haya

    Málaga, ESP, 29010

  • Hospital Universitario Central de Asturias

    Oviedo, ESP, 33013

  • Hospital Universitario Marques de Valdecilla

    Santander, ESP, 39008

  • Hospital ClÃ-nico Universitario de Santiago-CHUS

    Santiago de Compostela, ESP, 15706

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

France13 sites

  • CHU Besancon

    Besançon, Franche-Comte, 25000

  • Institut Bergonie

    Bordeaux, FRA, 33000

  • Unicancer

    Caen, FRA, 14000

  • Centre Georges-Francois Leclerc

    Dijon, FRA, 21000

  • ICM-Val d'Aurelle

    Montpellier, FRA, 34298

  • Saint-Louis Hospital

    Paris, FRA, 75010

  • Hopital St Antoine

    Paris, FRA, 75012

  • Hopital Pitie Salptriere

    Paris, FRA, 75013

  • CHU Poitiers

    Poitiers, FRA, 86000

  • Centre hospitalier Annecy Genevois

    Pringy, FRA, 74370

  • Centre Hospitalier Universitaire CHU de Rennes - Hopital de Pontchaillou

    Rennes, FRA, 35033

  • Institut de cancerologie Strasbourg-Europe

    Strasbourg, FRA, 67033

  • Institut Gustave Roussy

    Villejuif, Paris, 94805

Other trials in France

Germany13 sites

  • HELIOS Klinikum Berlin-Buch Saarow

    Berlin, DEU, 13125

  • Charite - Universitaetsmedizin Berlin

    Berlin, DEU, 13353

  • Universitaetsklinik Dresden

    Dresden, DEU, 1307

  • Universitaetsklinikum Erlangen

    Erlangen, Bavaria, 91054

  • University Hospital Essen

    Essen, DEU, 45147

  • Institut fr Klinisch Onkologische ForschungKrankenhaus Nordwest GmbH

    Frankfurt am Main, DEU, 60488

  • Haematologisch-Onkologische Praxis Hamburg Eppendorf

    Hamburg, DEU, 20249

  • Asklepios Tumorzentrum Hamburg AK Altona

    Hamburg, DEU, 22763

  • Universitaeres Krebszentrum Leipzig

    Leipzig, DEU, 4103

  • RKH Kliniken

    Ludwigsburg, DEU, 22763

  • Universitaetsmedizin Mannheim- III. Medizinische Klinik

    Mannheim, DEU, 68167

  • Klinikum Neuperlach

    München, DEU, 81737

  • Zentrum für Hämatologie und Onkologie MVZ GmbH

    Porta Westfalica, DEU, 32457

Other trials in Germany

Belgium11 sites

  • Onze-Lieve-Vrouwziekenhuis OLV - Campus Aalst

    Aalst, BEL, 9300

  • UCL St-Luc

    Brussels, BEL, 1200

  • Grand Hopital de Charleroi

    Charleroi, BEL, 6000

  • UZ Antwerpen

    Edegem, BEL, 2650

  • Centres Hospitaliers Jolimont

    Haine-Saint-Paul, BEL, 7100

  • UZ Leuven

    Leuven, BEL, 3000

  • Clinique CHC MontLegia

    Liège, Wallonia, 4000

  • CHU de Lige - Domaine Universitaire du Sart Tilman

    Liège, Wallonia, 4001

  • AZ Delta Roeselare

    Roeselare, BEL, 8800

  • AZ Turnhout

    Turnhout, BEL, 2300

  • CHU Mont-Godinne

    Yvoir, BEL, 5530

Other trials in Belgium

Hungary11 sites

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

    Budapest, HUN, 1097

  • National Institute of Oncology

    Budapest, HUN, 1122

  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest, HUN, H-1062

  • Debreceni Egyetem Klinikai Kozpont

    Debrecen, HUN, 4032

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

    Gyula, 5700

  • Somogy Megyei Kaposi Mor Oktato Korhaz, Klinikai Onkologiai Osztaly

    Kaposvár, Somogy County, 7400

  • Bacs- Kiskun Megyei Korhaz

    Kecskemét, HUN, 6000

  • Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz

    Nyíregyháza, HUN, 4400

  • Hetenyi G Korhaz, Onkologiai Kozpont

    Szolnok, HUN, 5004

  • Szent Borbala Korhaz

    Tatabánya, HUN, 2800

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

    Zalaegerszeg, Zala County, 8900

Other trials in Hungary

Italy11 sites

  • Fondazione Poliambulanza Hospital

    Brescia, ITA, 25124

  • Policlinico San Martino di Genova

    Genova, ITA, 16132

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, ITA, 20133

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, ITA, 20162

  • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

    Naples, ITA, 80131

  • Istituto Oncologico Veneto Irccs

    Padova, ITA, 35128

  • Azienda Ospedaliero Universitaria Pisana

    Pisa, ITA, 56126

  • Azienda USL-IRCCS di Reggio Emilia

    Reggio Emilia, ITA, 42123

  • Istituto Clinico Humanitas

    Rozzano MI, Lombardy, 20089

  • AO Card G Panico

    Tricase, ITA, 73039

  • Ospedale San Bortolo Azienda ULSS8 Berica - Distretto Est

    Vicenza, ITA, 36100

Other trials in Italy

Japan10 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • Kyushu Cancer Center

    Fukuoka, Fukuoka, 811-1395

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

  • St. Marianna University School of Medicine Hospital

    Kawasaki-shi, Kanagawa, 216-8511

  • Shikoku Cancer Center

    Matsuyama, Ehime, 791-0280

  • Aichi Cancer Center

    Nagoya, Aichi-ken, 464-8681

  • Kindai University Hospital

    Osakasayama-shi, Osaka, 589-8511

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • Shizuoka Cancer Center

    Shizuoka, Sunto-gun, 411-8777

  • Osaka University Hospital

    Suita-shi, Osaka, 565-0871

Other trials in Japan

Australia6 sites

  • The Queen Elizabeth Hospital

    Adelaide, South Australia, 5011

  • Flinders Medical Centre

    Adelaide, South Australia, 5042

  • Integrated Clinical Oncology Network Pty Ltd (Icon)

    Brisbane, Queensland, 4001

  • Western Health

    Melbourne, Victoria, 3021

  • Austin Hopistal Medical Oncology Unit

    Melbourne, Victoria, 3084

  • Monash Health

    Melbourne, Victoria, 3168

Other trials in Australia

Austria6 sites

  • Ordensklinikum Linz Barmherzige Schwestern

    Linz, AUT, 4010

  • Schwerpunktkrankenhaus Feldkirch

    Rankweil, AUT, 6830

  • Klinikum Steyr

    Steyr, AUT, 4400

  • Wiener Gesundheitsverbund - Klinik Ottakring

    Vienna, AUT, 1160

  • Klinikum Wels-Grieskirchen GmbH

    Wels, AUT, 4600

  • Landesklinikum Wiener Neustadt

    Wiener Neustadt, AUT, 2700

Other trials in Austria

Czechia3 sites

  • Masaryk Memorial Cancer Institute, Hematoonkologie

    Brno, Moravia, 60200

  • Fakultni nemocnice Olomouc, Onkologicka klinika

    Olomouc, Moravia, 77900

  • Vseobecna Fakultni Nemocnice VFN, Onkologicka Klinika

    Prague, 12808

Other trials in Czechia

Estonia3 sites

  • East Tallinn Central Hospital Centre of Oncology

    Tallinn, Harju, 11312

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

    Tallinn, Harju, 13419

  • Tartu University Hospital Clinic of Haematology and Oncology

    Tartu, 50406

Other trials in Estonia

United Kingdom3 sites

  • Aberdeen Royal Infirmary

    Aberdeen, GBR, AB25 2ZN

  • The Royal Marsden Hospital

    London, GBR, SW3 6JJ

  • Sarah Cannon Research Institute UK

    London, Middlesex, W1G 6AD

Other trials in United Kingdom

Poland2 sites

  • Bialostockie Centrum Onkologii im. Marii Skodowskiej-Curie

    Bialystok, Podlaskie Voivodeship, 15-027

  • M Sklodowska Curie Memorial Cancer Center, Klinika Gastroenterologii Onkologicznej

    Warsaw, Masovia, 02034

Other trials in Poland

About this study

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

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.

Read the 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.

Being tested
Fruquintinib, Placebo
Keywords
colon, colorectal, mcrc, crc, metastatic colon, metastatic colorectal, VEGF, VEGFR
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FruquintinibDrug

    Also called HMPL-013

    Oral VEGFR inhibitor

  • PlaceboDrug

    Placebo capsule

Study groups in NCT04322539
Study groupRoleWhat they receive
Fruquintinib Plus Best Supportive Care (BSC) GroupExperimentalParticipants 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).
Receives: Drug: Fruquintinib
Placebo Plus BSC GroupPlacebo comparatorParticipants 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    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.

    Measured: From date of randomization to death from any cause (up to 22 months)

Secondary outcomes (15)

  1. Progression Free Survival (PFS), as Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

    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.

    Measured: From randomization until the first documentation of objective progression or death, whichever comes first (up to 22 months)

  2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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).

    Measured: From randomization until the first documentation of best overall response (up to 22 months)

  3. Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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.

    Measured: From randomization until the first documentation of best overall response (up to 22 months)

  4. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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.

    Measured: From first occurrence of PR or CR until the first documentation progression or death, whichever comes first (up to 22 months

  5. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    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 30 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.

    Measured: From start of study drug administration up to approximately 40 months

  6. Observed Plasma Concentrations of Fruquintinib and Metabolite M11

    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.

    Measured: 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)

  7. Change From Baseline of Electrocardiogram (ECG) Results - QTcF Intervals Using Fridericia's Formula

    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.

    Measured: 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)

  8. Change From Baseline of ECG Results -QTcB Intervals Using Bazzett's Formula

    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.

    Measured: 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)

  9. Correlation Between Fruquintinib Exposure (CminSS) and Efficacy Parameters (OS)

    Model-predicted steady-state minimum plasma concentrations (CminSS) of fruquintinib based on the starting dose or adjusted for relative dose intensity [RDI] were used as the exposure measures in the efficacy exposure-response analyses. The correlation between OS and exposure was estimated using multivariable Cox proportional hazards modeling. OS was analyzed as time-to-event variable using a survival model. The efficacy exposure-response analyses included participants with mCRC and pooled the data from the fruquintinib group of current Study 2019-013-GLOB1 (N=328) and from Cohort B of Study 2015-013-00US1 (NCT03251378) (N=40) as per planned analysis. Here, the "unit of measure" i.e., '1/(nanogram per milliliter [ng/mL])', corresponds to the coefficient that describes the relationship between the probability of survival and CminSS value.

    Measured: Up to 22 months

  10. Correlation Between Fruquintinib Exposure (CmaxSS) and Safety Parameters (Any Grade [Gr] and Grade 3+ (Gr3+): Dermatological Toxicity, Proteinuria and Gr Hemorrhage)

    Model-predicted steady-state maximum plasma concentration (CmaxSS) of fruquintinib based on the assigned dose of fruquintinib were investigated as fruquintinib exposure measure for the safety exposure-response analyses. The correlation between exposure and the probability of experiencing these AEs was evaluated using logistic regression analysis, with the slope serving as the estimate. The safety exposure-response analysis included participants with cancer, and the data of this outcome measure were pooled with data from the following studies as per the planned analysis: 2019-013-GLOB1 (NCT04322539) (N=334), 2009-013-00CH1 (NCT01645215) (N=40), 2012-013-00CH3 (NCT01975077) (N=40), and 2015-013-00US1 (NCT03251378) (N=101). Here, the "unit of measure" i.e., '1/(ng/mL)', corresponds to the coefficient that describes the relationship between the probability of occurrence of the safety parameter and CmaxSS value.

    Measured: Up to 22 months

  11. 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

    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 worsened. 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.

    Measured: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)

  12. Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Visual Analog Scale (VAS) Score

    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 worsened. Change from baseline in the EQ-5D-5L VAS scores was performed by visit (i.e. cycle), using a REML-based MMRM approach.

    Measured: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)

  13. Change From Baseline in EuroQoL 5 Dimension 5 Level (EQ-5D-5L) Health Utility Index Scores

    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.

    Measured: Baseline, Cycle 2, 3 and 4 (Each cycle=28 days)

  14. Health Care Resource Utilization: Duration of Hospital Visits by Participants

    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.

    Measured: From start of study drug administration up to 22 months

  15. Health Care Resource Utilization: Number of Participants With Any Concomitant Medications Prescribed

    Number of participants with any concomitant medications prescribed were reported.

    Measured: From start of study drug administration up to 22 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2020
  2. Study start12 Aug 2020
  3. Primary completion29 Jul 2022
  4. Study completion24 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
691 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04322539
Sponsor's protocol ID
2019-013-GLOB1
Acronym
FRESCO-2
Status last verified
Mar 2025
First submitted
24 Mar 2020
Last updated
4 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kotani D, Yoshino T, Masuishi T, Sunakawa Y, Takashima A, Yamazaki K, Kawakami H, Nishina T, Komatsu Y, Esaki T, Eng C, Ukrainskyj S, Pallai R, Nanda S, Yang Z, Schelman W, Kania M, Satoh T. Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer: a FRESCO-2 subgroup analysis of patients enrolled in Japan. Int J Clin Oncol. 2025 Oct;30(10):2043-2052. doi: 10.1007/s10147-025-02852-9. Epub 2025 Sep 1.

    PubMed 40888992

  • Zhou X, Toms A, Morton D, Wang X, Taylor A, Dasari A, Gupta N, Chien C. Assessment of the Effects of Fruquintinib on Cardiac Safety in Patients with Metastatic Colorectal Cancer. J Clin Pharmacol. 2025 Nov;65(11):1411-1419. doi: 10.1002/jcph.70051. Epub 2025 Jun 8.

    PubMed 40485075

  • Eng C, Dasari A, Lonardi S, Garcia-Carbonero R, Elez E, Yoshino T, Sobrero A, Yao J, Garcia-Alfonso P, Kocsis J, Gracian AC, Sartore-Bianchi A, Satoh T, Randrian V, Tomasek J, Chong G, Yang Z, Guevara F, Schelman W, Pallai R, Tabernero J. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer: safety analysis of FRESCO-2. Oncologist. 2025 Mar 10;30(3):oyae360. doi: 10.1093/oncolo/oyae360.

    PubMed 40163688

  • Sobrero A, Dasari A, Aquino J, Lonardi S, Garcia-Carbonero R, Elez E, Yoshino T, Yao J, Garcia-Alfonso P, Kocsis J, Gracian AC, Sartore-Bianchi A, Satoh T, Randrian V, Tomasek J, Chong G, Price T, Yu Z, Geiger A, Chen L, Yang Z, Schelman WR, Kania M, Tabernero J, Eng C. Health-related quality of life associated with fruquintinib in patients with metastatic colorectal cancer: Results from the FRESCO-2 study. Eur J Cancer. 2025 Mar 11;218:115268. doi: 10.1016/j.ejca.2025.115268. Epub 2025 Jan 29.

    PubMed 39952149

  • Dasari A, Lonardi S, Garcia-Carbonero R, Elez E, Yoshino T, Sobrero A, Yao J, Garcia-Alfonso P, Kocsis J, Cubillo Gracian A, Sartore-Bianchi A, Satoh T, Randrian V, Tomasek J, Chong G, Paulson AS, Masuishi T, Jones J, Csoszi T, Cremolini C, Ghiringhelli F, Shergill A, Hochster HS, Krauss J, Bassam A, Ducreux M, Elme A, Faugeras L, Kasper S, Van Cutsem E, Arnold D, Nanda S, Yang Z, Schelman WR, Kania M, Tabernero J, Eng C; FRESCO-2 Study Investigators. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023 Jul 1;402(10395):41-53. doi: 10.1016/S0140-6736(23)00772-9. Epub 2023 Jun 15.

    PubMed 37331369

  • 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.

    PubMed 33993740

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fruquintinib in people with Metastatic Colorectal Cancer and Metastatic Colon Cancer, run by Hutchison Medipharma Limited at 153 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 153 sites in United States, Spain, France, Germany, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: From date of randomization to death from any cause (up to 22 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04322539, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025.

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