Clinical trial NCT01607957: Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Refractory, metastatic colorectal cancer
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2012-05-30
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 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 outcomes:
measure: Progression-free Survival
timeFrame: 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)
measure: Percentage of Participants With Adverse Events (AE), Treatment-Related AEs, Discontinuations, Serious Adverse Events (SAEs) and Deaths
timeFrame: 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
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Fresno
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Gilroy
country: United States
facility: Ronald H. Yanagihara, MD
state: California
city: Los Angeles
country: United States
facility: LAC and USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Pacific Hematology Oncology Associates
state: California
city: San Jose
country: United States
facility: San Jose Medical Group
state: California
city: San Luis Obispo
country: United States
facility: Coastal Integrative Cancer Care
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Orlando
country: United States
facility: MD Anderson Cancer Center Orlando
state: Florida
city: Peoria
country: United States
facility: Illinois Cancer Care, P.C.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Fndtn
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Jefferson City
country: United States
facility: Jefferson City Medical Group
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Sylvania
country: United States
facility: Hickman Cancer Center at Flower Hospital
state: Ohio
city: Fredericksburg
country: United States
facility: Hematology/Oncology Associates of Fredericksburg
state: Virginia
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elisabeth Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Linz
country: Austria
facility: Krankenhaus der Barmherzigen Schwestern Linz
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: Universitaet Wien
city: Wien
country: Austria
facility: Universitaetsklinik fur Innere Medizin
city: Wien
country: Austria
facility: Wilhelminenspital Wien
city: Brussels
country: Belgium
facility: Cliniques Universitaires UCL St. Luc
city: Brussels
country: Belgium
facility: Erasme University Hospital-ULB-Brussels
city: Charleroi
country: Belgium
facility: Grand Hospital de Charleroi
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Edegem
country: Belgium
facility: University Hospital Gent
city: Gent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Leuven University Hospital - Campus Gasthuiseberg
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
city: Hradec Kralove
country: Czechia
facility: Klinika onkologie a radioteraie, Facultni nemocnice Hradec Kralove
city: Nova Ves pod Plesi
country: Czechia
facility: Institute of Oncology and Rehabilitation Ples
city: Besancon
country: France
facility: CHU de Becançon
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Lille
country: France
facility: Centre Oscar Lambret
city: Montpellier
country: France
facility: CRLC Val d'Aurelle
city: Paris cedex 12
country: France
facility: Hopital Saint Antoine
city: Rennes cedex
country: France
facility: Centre Eugene Marquis
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfuerstendamm
city: Bonn
country: Germany
facility: Praxiskooperation Bonn-Euskirchen-Rheinbach
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus - Dresden
city: Frankfurt
country: Germany
facility: Medizinische Klinik am Krankenhaus Nordwest GmbH
city: Halle (Saale)
country: Germany
facility: Uniklinik der Martin-Luther-Universitaet Halle-Wittenberg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Koeln
country: Germany
facility: Uniklinik Koeln
city: Mainz
country: Germany
facility: Johannes Gutenberg Universität Mainz
city: Mannheim
country: Germany
facility: Interdisziplinaeres Tumorzentrum Mannheim
city: Muenchen
country: Germany
facility: Staedtisches Klinikum Muenchen / Klinikum Neuperlach
city: München
country: Germany
facility: Klinikum der Universität München - Großhadern
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Dublin
country: Ireland
facility: Adelaide and Meath Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
state: Lombardy
city: Genova
country: Italy
facility: Universita Delgi Studi de Genova (UNIGE)- Azienda Ospedaliera. Universitaria "San Martino" (Ospedale San Martino)
city: Milano
country: Italy
facility: Fondazione IRCCS Instituto Nazionale dei Tumori Milano
city: Milan
country: Italy
facility: A.O. Ospedale Niguarda Ca' Granda
city: Naples
country: Italy
facility: A.O. R.N. "A.Cardarelli"
city: Napoli
country: Italy
facility: Seconda Universita degli Studi de Napoli
city: Orbassano
country: Italy
facility: AOU San Luidi di Orbassano
city: Pisa
country: Italy
facility: Azienda Ospedaliero
city: Reggio Emilia
country: Italy
facility: Arcispidale S Maria Nuova
city: Rimini
country: Italy
facility: Ospedale di Rimini
city: Sondrio
country: Italy
facility: Ospedale di Sondrio
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: KKR Sapporo Medical Center TONAN-Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tsukuba
country: Japan
facility: Tsukuba University Hospital
state: Ibaraki
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Takatsuki
country: Japan
facility: Osaka Medical College Hospital
state: Osaka
city: Kita-adachi-gun
country: Japan
facility: Saitama Cancer Center
state: Saitama
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Shimotsuke
country: Japan
facility: Jichi Medical University Hospital
state: Tochigi
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Chiba
country: Japan
facility: Chiba Cancer Center
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz - Universidad Autonoma de Madrid
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Carlos Haya
city: Murcia
country: Spain
facility: Hospital Universitario Morales Messeguer
city: Sabadell
country: Spain
facility: Corporacion Sanitaria Parc Tauli
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: St James' Institute of Oncology
city: London
country: United Kingdom
facility: University College London Hospitals Foundation NHS Trust
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Dana-Farber Cancer Institute
name: From - Boston, MA
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Gasthuisberg
name: From - Leuven, Belgium
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Center Hospital East
name: From - Kashiwa, Chiba Japan
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.