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

Colorectal Cancer Clinical Trial

— RECOURSE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01607957
• Other study ID #: TPU-TAS-102-301
• Secondary ID: 2012-000109-66
• Status: Completed
• Phase: Phase 3
• Start date: June 17, 2012
• Est. completion date: May 23, 2016

Study information

• Verified date: June 2020
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: May 23, 2016
• Est. primary completion date: January 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  France,  Germany,  Ireland,  Italy,  Japan,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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