Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies (RECOURSE)

Randomized, Double-blind, Phase 3 Study of TAS-102 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies

The purpose of this study is to compare the efficacy and safety of TAS-102 versus placebo in patients with refractory metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: TAS-102; Drug: Placebo

Detailed Description

This is a multinational, double-blind, two-arm, parallel, randomized Phase 3 comparison study evaluating the efficacy and safety of TAS-102 versus placebo in patients with refractory metastatic colorectal cancer. Patients will be randomly assigned (2:1) to TAS-102 (experimental arm) or placebo (control arm).

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elisabeth Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Austria
  • Linz, Austria, 4010
    • Krankenhaus der Barmherzigen Schwestern Linz
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen GmbH
  • Wien, Austria, 1160
    • Wilhelminenspital Wien
  • Wien, Austria, 1090
    • Universitaet Wien
  • Wien, Austria, 1090
    • Universitaetsklinik fur Innere Medizin
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires UCL St. Luc
  • Brussels, Belgium, B-1070
    • Erasme University Hospital-ULB-Brussels
  • Charleroi, Belgium, 6000
    • Grand Hospital de Charleroi
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Edegem, Belgium, 2650
    • University Hospital Gent
  • Gent, Belgium, 9000
    • University Hospital Gent
  • Leuven, Belgium, 3000
    • University Hospital Gasthuisberg
  • Leuven, Belgium, 3000
    • Leuven University Hospital - Campus Gasthuiseberg
• Czechia
  • Hradec Kralove, Czechia, 50005
    • Klinika onkologie a radioteraie, Facultni nemocnice Hradec Kralove
  • Nova Ves pod Plesi, Czechia, 26204
    • Institute of Oncology and Rehabilitation Ples
• France
  • Besancon, France, 25030
    • CHU de Becançon
  • Bordeaux, France, 33075
    • University Hospital of Bordeaux
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Montpellier, France, 34298
    • CRLC Val d'Aurelle
  • Paris cedex 12, France, 75571
    • Hopital Saint Antoine
  • Rennes cedex, France, 35042
    • Centre Eugène Marquis
• Germany
  • Berlin, Germany, 10707
    • Onkologische Schwerpunktpraxis Kurfuerstendamm
  • Bonn, Germany, 53123
    • Praxiskooperation Bonn-Euskirchen-Rheinbach
  • Dresden, Germany, 1307
    • Universitatsklinikum Carl Gustav Carus - Dresden
  • Frankfurt, Germany, 60488
    • Medizinische Klinik am Krankenhaus Nordwest GmbH
  • Halle (Saale), Germany, 6120
    • Uniklinik der Martin-Luther-Universitaet Halle-Wittenberg
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Koeln, Germany, 50937
    • Uniklinik Koeln
  • Mainz, Germany, 55131
    • Johannes Gutenberg Universitat Mainz
  • Mannheim, Germany, 68167
    • Interdisziplinaeres Tumorzentrum Mannheim
  • Muenchen, Germany, 81737
    • Staedtisches Klinikum Muenchen / Klinikum Neuperlach
  • München, Germany, 81377
    • Klinikum der Universität München - Großhadern
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg gGmbH
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• Ireland
  • Cork, Ireland
    • Bon Secours Hospital
  • Dublin, Ireland, 4
    • St. Vincent's University Hospital
  • Dublin, Ireland, 24
    • Adelaide and Meath Hospital
• Italy
  • Genova, Italy, 16132
    • Universita Delgi Studi de Genova (UNIGE)- Azienda Ospedaliera. Universitaria "San Martino" (Ospedale San Martino)
  • Milan, Italy, 20162
    • A.O. Ospedale Niguarda Ca' Granda
  • Milano, Italy, 20133
    • Fondazione IRCCS Instituto Nazionale dei Tumori Milano
  • Naples, Italy, 80131
    • A.O. R.N. "A.Cardarelli"
  • Napoli, Italy, 80131
    • Seconda Universita degli Studi de Napoli
  • Orbassano, Italy, 1010043
    • AOU San Luidi di Orbassano
  • Pisa, Italy, 6756126
    • Azienda Ospedaliero
  • Reggio Emilia, Italy, 42123
    • Arcispidale S Maria Nuova
  • Rimini, Italy, 47923
    • Ospedale di Rimini
  • Sondrio, Italy, 23100
    • Ospedale di Sondrio
  • Lombardy
    • Brescia, Lombardy, Italy, 25124
      • Fondazione Poliambulanza
• Japan
  • Chiba, Japan, 2608717
    • Chiba Cancer Center
  • Fukuoka, Japan, 8111395
    • National Hospital Organization Kyushu Cancer Center
  • Kumamoto, Japan, 8608556
    • Kumamoto University Hospital
  • Osaka, Japan, 5378511
    • Osaka Medical Center for Cancer and Cardiovascular Diseases
  • Tokushima, Japan, 7708503
    • Tokushima University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 4648681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-0882
      • National Cancer Center Hospital East
    • Kashiwa, Chiba, Japan, 2778577
      • National Cancer Center Hospital East
  • Ehime
    • Matsuyama, Ehime, Japan, 7910280
      • National Hospital Organization Shikoku Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 0608648
      • Hokkaido University Hospital
    • Sapporo, Hokkaido, Japan, 0600001
      • KKR Sapporo Medical Center TONAN-Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 6500047
      • Kobe City Medical Center General Hospital
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 3058576
      • Tsukuba University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 2418515
      • Kanagawa Cancer Center
  • Osaka
    • Takatsuki, Osaka, Japan, 5698686
      • Osaka Medical College Hospital
  • Saitama
    • Kita-adachi-gun, Saitama, Japan, 3620806
      • Saitama Cancer Center
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 4118777
      • Shizuoka Cancer Center
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 3290498
      • Jichi Medical University Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan, 1358550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
    • Shinjuku-ku, Tokyo, Japan, 1608582
      • Keio University Hospital
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Lleida, Spain, 25198
    • Hospital Arnau de Vilanova
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz - Universidad Autonoma de Madrid
  • Malaga, Spain, 29010
    • Hospital Carlos Haya
  • Murcia, Spain, 30008
    • Hospital Universitario Morales Messeguer
  • Sabadell, Spain, 8916
    • Corporacion Sanitaria Parc Tauli
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska University Hospital
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Bristol, United Kingdom, BS2 8ED
    • University Hospitals Bristol NHS Foundation Trust
  • Leeds, United Kingdom, LS9 7TF
    • St James' Institute of Oncology
  • London, United Kingdom, NW1 2PG
    • University College London Hospitals Foundation NHS Trust
  • Surrey, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Center for Cancer Care
  • California
    • Fresno, California, United States, 93720
      • California Cancer Associates For Research and Excellence
    • Gilroy, California, United States, 95020
      • Ronald H. Yanagihara, MD
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • LAC and USC Medical Center
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
    • San Jose, California, United States, 95124
      • San Jose Medical Group
    • San Luis Obispo, California, United States, 93401
      • Coastal Integrative Cancer Care
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Cancer Care, P.C.
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • New Orleans, Louisiana, United States, 70121-2429
      • Ochsner Clinic Fndtn
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
  • Missouri
    • Jefferson City, Missouri, United States, 65109-6023
      • Jefferson City Medical Group
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Sylvania, Ohio, United States, 43560
      • Hickman Cancer Center at Flower Hospital
  • Virginia
    • Fredericksburg, Virginia, United States, 22408
      • Hematology/Oncology Associates of Fredericksburg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Has provided written informed consent
2. Has adenocarcinoma of the colon or rectum
3. Has failed at least 2 prior regimens of standard chemotherapies for metastatic colorectal cancer
4. ECOG performance status of 0 or 1
5. Is able to take medications orally
6. Has adequate organ function (bone marrow, kidney and liver)
7. Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control.

Exclusion Criteria:

1. Certain serious illnesses or medical condition(s)
2. Has had certain other recent treatment e.g. major surgery, anticancer therapy, extended field radiation, received investigational agent, within the specified time frames prior to study drug administration
3. Has received TAS-102
4. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies
5. Is a pregnant or lactating female

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablets, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria are met.
Experimental: TAS-102	Drug: TAS-102; 35 mg/m2/dose, orally, twice daily on days 1-5 and 8-12 of each 28-day cycle. Number of cycles: until at least one of the discontinuation criteria are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as the time from the date of randomization to the date of death for participants. If a participant discontinued study medication for reasons other than radiologic disease progression, the participant was followed for tumor response until radiologic disease progression or initiation of new anticancer therapy.	Every 8 weeks, up to 12 months after the last participant was randomized or until the target number of events (deaths) was met, whichever was later. (Overall survival data was collected till 24 Jan 2014 which was date of observation of the 571st death)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Tumor assessments were performed throughout the study based on RECIST, Version 1.1, 2009. Progression free survival was defined as the time (in months) from the date of randomization until the date of the investigator-assessed radiological disease progression or death due to any cause. For participants who were alive with no radiological disease progression as of the analysis cut-off date, their survival was censored at the date of the last tumor assessment. Participants who received non-study cancer treatment before disease progression, or participants with clinical but not radiologic evidence of progression, were censored at the date of the last radiologic evaluable tumor assessment before the non-study cancer treatment was initiated.	Every 8 weeks, up to 12 months after the last participant was randomized or until the date of the investigator-assessed radiological disease progression or death due to any cause,whichever was later. (Progression free survival cutoff: 31 Jan 2014)
Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AEs were events between administration of study drug and up to 30 Days that were absent before treatment or that worsened relative to pre-treatment state. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability /incapacity; congenital anomaly. The AEs were graded for severity using National Cancer Institute Common Terminology Criteria for AEs.	From the time of signing the informed consent form until the period of participant follow up (30 days following after the administration of last dose of study medication or until initiation of new antitumor therapy, whichever was earlier

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.
• Investigators: Principal Investigator: From - Boston, MA, Dana-Farber Cancer Institute; Principal Investigator: From - Leuven, Belgium, University Hospital, Gasthuisberg; Principal Investigator: From - Kashiwa, Chiba Japan, National Cancer Center Hospital East

Publications and helpful links

General Publications

• Yoshino T, Cleary JM, Van Cutsem E, Mayer RJ, Ohtsu A, Shinozaki E, Falcone A, Yamazaki K, Nishina T, Garcia-Carbonero R, Komatsu Y, Baba H, Argiles G, Tsuji A, Sobrero A, Yamaguchi K, Peeters M, Muro K, Zaniboni A, Sugimoto N, Shimada Y, Tsuji Y, Hochster HS, Moriwaki T, Tran B, Esaki T, Hamada C, Tanase T, Benedetti F, Makris L, Yamashita F, Lenz HJ. Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials. Ann Oncol. 2020 Jan;31(1):88-95. doi: 10.1016/j.annonc.2019.10.005.
• Van Cutsem E, Mayer RJ, Laurent S, Winkler R, Gravalos C, Benavides M, Longo-Munoz F, Portales F, Ciardiello F, Siena S, Yamaguchi K, Muro K, Denda T, Tsuji Y, Makris L, Loehrer P, Lenz HJ, Ohtsu A; RECOURSE Study Group. The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer. Eur J Cancer. 2018 Feb;90:63-72. doi: 10.1016/j.ejca.2017.10.009. Epub 2017 Dec 21.
• Longo-Munoz F, Argiles G, Tabernero J, Cervantes A, Gravalos C, Pericay C, Gil-Calle S, Mizuguchi H, Carrato-Mena A, Limon ML, Garcia-Carbonero R. Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial. Clin Transl Oncol. 2017 Feb;19(2):227-235. doi: 10.1007/s12094-016-1528-7. Epub 2016 Jul 21.
• Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. doi: 10.1056/NEJMoa1414325.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2012
• Primary Completion (Actual): January 31, 2014
• Study Completion (Actual): May 23, 2016

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 25, 2012
• First Posted (Estimate): May 30, 2012

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: June 1, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Refractory, metastatic colorectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: TPU-TAS-102-301; 2012-000109-66 (EudraCT Number)