Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients

NCT ID: NCT04737187

Last Updated: 2024-09-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

492 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-25

Study Completion Date

2023-09-12

Brief Summary

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This study is designed as an international, open-label, controlled two-arm, randomized phase III comparison study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC.

Detailed Description

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This is an international, open-label, controlled two-arm, randomised phase III study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC. The analysis will be done after 331 events are reported. In order to observe this number of events, 490 patients will be randomised (1:1) to receive trifluridine/tipiracil in combination with bevacizumab (experimental arm) or trifluridine/tipiracil monotherapy (control arm).

Conditions

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Refractory Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trifluridine/Tipiracil + Bevacizumab

Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 an Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram \[mg/kg\], intravenous \[IV\] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.

Group Type EXPERIMENTAL

Trifluridine/Tipiracil

Intervention Type DRUG

Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest

Bevacizumab

Intervention Type DRUG

administered every 2 weeks (Day 1 and Day 15)

Trifluridine/Tipiracil

Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.

Group Type ACTIVE_COMPARATOR

Trifluridine/Tipiracil

Intervention Type DRUG

Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest

Interventions

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Trifluridine/Tipiracil

Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest

Intervention Type DRUG

Bevacizumab

administered every 2 weeks (Day 1 and Day 15)

Intervention Type DRUG

Other Intervention Names

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TAS102 S 95005 Lonsurf Avastin

Eligibility Criteria

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Inclusion Criteria

1. Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded).
2. RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy.
3. Has received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen.
4. Has measurable or non-measurable disease as defined by RECIST version 1.1
5. Is able to swallow oral tablets.
6. Estimated life expectancy ≥12 weeks.
7. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1

Exclusion Criteria

1. More than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer.
2. Pregnancy, lactating female or possibility of becoming pregnant during the study.
3. Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization.
4. Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation).
5. Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
6. Has severe or uncontrolled active acute or chronic infection.
7. Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
8. Known Hepatitis B or Hepatitis C Virus infection.
9. Known carriers of HIV antibodies.
10. Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia.
11. Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization.
12. Treatment with any of the following within the specified time frame prior to randomization:

* major surgery within 4 weeks prior to randomisation (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study
* Prior radiotherapy if completed less than 4 weeks before randomisation, except if provided as a short course for symptoms palliation only.
* Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks prior to randomization
13. Other clinically significant medical conditions.
14. Other malignancies.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut de Recherches Internationales Servier

OTHER

Sponsor Role collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Josep Tabernero, Prof

Role: PRINCIPAL_INVESTIGATOR

Vall d'Hebron Institute of Oncology

Locations

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Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

City of Hope - South Pasedena

South Pasadena, California, United States

Site Status

City of Hope - Upland

Upland, California, United States

Site Status

Mayo Clinic - FL

Jacksonville, Florida, United States

Site Status

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status

Comprehensive Hematology Oncology

St. Petersburg, Florida, United States

Site Status

DuPage Medical Group - Joliet Oncology-Hematology Associates

Joliet, Illinois, United States

Site Status

Investigative Clinical Research of Indiana LLC

Noblesville, Indiana, United States

Site Status

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status

Mayo Clinic - Rochester

Rochester, New York, United States

Site Status

Renovatio Clinical - El Paso

El Paso, Texas, United States

Site Status

"Medizinische Universität Graz "

Graz, , Austria

Site Status

"Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V"

Innsbruck, , Austria

Site Status

"Ordensklinikum Linz Barmherzige Schwestern Interne I"

Linz, , Austria

Site Status

"Landeskrankenhaus Feldkirch Interne E"

Rankweil, , Austria

Site Status

"Landeskrankenhaus (SALK) Universitätsklinik für Innere Medizin III (SALK)"

Salzburg, , Austria

Site Status

"Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie"

Vienna, , Austria

Site Status

"Landesklinikum Wiener Neustadt "

Wiener Neustadt, , Austria

Site Status

"OLV Ziekenhuis Oncology"

Aalst, , Belgium

Site Status

"Universitair Ziekenhuis Antwerpen Oncologie"

Edegem, , Belgium

Site Status

"UZ Leuven Campus Gasthuisberg Digestieve Oncologie"

Leuven, , Belgium

Site Status

"CHC Montlégia Oncologie"

Liège, , Belgium

Site Status

"AZ NIKOLAAS Oncology"

Sint-Niklaas, , Belgium

Site Status

"Hospital do Câncer de Barretos - Fundação Pio XII Unidade de Pesquisa Clínica"

Barretos, , Brazil

Site Status

"Hospital de Base Centro Integrado de Pesquisa"

São José do Rio Preto, , Brazil

Site Status

"ICESP - Instituto do Câncer do Estado de São Paulo Centro Integrado de Pesquisa"

São Paulo, , Brazil

Site Status

Hospital A C Camargo Unidade de Pesquisa Clinica Rua Antonio Prudente

São Paulo, , Brazil

Site Status

Hospital Sao Camilo Nucleo de Pesquisa Av Alcantara Machado

São Paulo, , Brazil

Site Status

Hospital Albert Einstein Instituto de Ensino e Pesquisa Av Albert Einstein

São Paulo, , Brazil

Site Status

"Aalborg Universitetshospital, Syd Onkologisk Afdeling"

Aalborg, , Denmark

Site Status

Rigshospitalet Dpt of Oncology

Copenhagen, , Denmark

Site Status

"Regionshospitalet Herning, Hospitalsenheden Vest Onkologisk Afdeling"

Herning, , Denmark

Site Status

"Odense Universitetshospital Department of Oncology"

Odense, , Denmark

Site Status

"CHU Jean Minjoz Service d'oncologie médicale"

Besançon, , France

Site Status

"CHU Morvan Institut de Cancérologie et d'Hématologie"

Brest, , France

Site Status

"Centre de lutte contre le cancer Francois Baclesse UCP Digestif"

Caen, , France

Site Status

Hôpital Saint-Antoine Service d'Oncologie Médicale

Paris, , France

Site Status

"Hôpital Européen Georges Pompidou Oncologie Hépatogastroenterologie-oncologie digestive"

Paris, , France

Site Status

CHU de Poitiers Pole Régional de Cancérologie

Poitiers, , France

Site Status

Onkologische Schwerpunktpraxis Kurfuerstendamm

Berlin, , Germany

Site Status

Charite Universitätsmedizin Medizinische Klinik m.S. Haemat., Onko., Tumorimmunologie

Berlin, , Germany

Site Status

Lübecker Onkologische Schwerpunktpraxis im Hochschulstadttei

Lübeck, , Germany

Site Status

Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III

München, , Germany

Site Status

Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly

Budapest, , Hungary

Site Status

Szent Imre Egyetemi Oktatokorhaz Klinikai Onkologiai Osztaly

Budapest, , Hungary

Site Status

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Onkologiai Intezet

Debrecen, , Hungary

Site Status

Petz Aladar Megyei Oktato Korhaz Onkoradiologiai Osztaly

Győr, , Hungary

Site Status

Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont

Kecskemét, , Hungary

Site Status

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kp. Onkoterápiás Klinika

Szeged, , Hungary

Site Status

JNSZ Megyei Hetenyi Geza Korhaz es Rendelointezet Megyei Onkologiai Centrum

Szolnok, , Hungary

Site Status

Markusovszky Egyetemi Oktatokorhaz Onkoradiologiai Osztaly

Szombathely, , Hungary

Site Status

Azienda Policlinico Universitaria - Presidio Monserrato Oncologia Medica Strada Statale 554 Sestu-Monserrato

Cagliari, Italiy, Italy

Site Status

A.O.U. Seconda Universita degli Studi di Napoli U.O.C di Oncologia Medica e di Ematologia Dipartimento Medico di Internistica clinca e sperimentale " F Magrassi - A. Lanzara" Via Sergio Pansisni ,

Napoli, , Italy

Site Status

Istituto Nazionale Tumori, I.R.C.C.S "Fondazione G Pascale" Struttura Complessa di Oncologia Medica Addominale

Napoli, , Italy

Site Status

Istituto Oncologico Veneto IOV - IRCCS Unita Operativa Complessa Oncologia Medica 1 Via Gattamelata 64

Padua, , Italy

Site Status

A.O.U. Pisana-Ospedale Santa Chiara U.O. di Oncologia Medica 2

Pisa, , Italy

Site Status

Ospedale San Carlo U.O. Oncologia Medica Via Potito Petrone, Ctr Macchia Romana

Potenza, , Italy

Site Status

Arcispedale Santa Maria Nuova Unità di Oncologia

Reggio Emilia, , Italy

Site Status

Istituto Clinico Humanita IRCCS Dipartimento di Oncologia Medica ed Ematologia Via Manzoni,

Rozzano (MI), , Italy

Site Status

IRCSS Casa Sollievo della Sofferenza Dipartimento Onco-Ematologia Vale Cappuccini 1

San Giovanni Rotondo, , Italy

Site Status

Przychodnia Lekarska "KOMED"

Konin, , Poland

Site Status

SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii

Krakow, , Poland

Site Status

Opolskie Centrum Onkologii im. Tadeusza Koszarowskiego Oddzial Onkologii Klinicznej

Opole, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.

Słupsk, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Klinika Onkologii i Radioterapii

Warsaw, , Poland

Site Status

Wojskowy Instytut Medyczny Klinika Onkologii

Warsaw, , Poland

Site Status

Centralny Szpital Kliniczny MSWiA Oddział Radioterapii i Onkologii

Warzszawa, , Poland

Site Status

Pan American Center for Oncology Trials, LLC

Río Piedras, Porto RICO, Puerto Rico

Site Status

Arkhangelsk Clinical Oncology Dispensary chemotherapy department

Arkhangelsk, , Russia

Site Status

Clinical Oncology Dispensary No.1 Chemotherapy Department

Krasnodar, , Russia

Site Status

Russian Cancer Research Center n.a. NN Blokhin Clinical Pharmacology and Chemotherapy

Moscow, , Russia

Site Status

University Headache Clinic Outpatient oncology clinic

Moscow, , Russia

Site Status

Moscow City Oncology Hospital # 62 chemotherapy department

Moscow Region, , Russia

Site Status

Omsk Clinical Oncologic Dispensary Chemotherapy

Omsk, , Russia

Site Status

Scientific Centre for Specialized Medical Care (oncological) Chemotherapy

Saint Petersburg, , Russia

Site Status

National Medical Research Center of Oncology N.N. Petrova

Saint Petersburg, , Russia

Site Status

Saint Petersburg City Oncology Clilnic

Saint Petersburg, , Russia

Site Status

Multidisciplinary clinic "Reaviz

Samara, , Russia

Site Status

Oncology dispensary No.2 Oncology department

Sochi, , Russia

Site Status

SBIH of YR "Clinical oncology hospital chemotherapy department"

Yaroslavl, , Russia

Site Status

"H. Valle de Hebrón Servicio de Oncología - (VHIR)"

Barcelona, , Spain

Site Status

"Hospital de la Santa Creu I Sant Pau Oncología Medica"

Barcelona, , Spain

Site Status

"Hospital Uni. Reina Sofía - Hospital Provincial Departamento de Oncología Médica"

Córdoba, , Spain

Site Status

"INSTITUTO CATALAN DE ONCOLOGÍA - ICO Oncología Médica"

L'Hospitalet de Llobregat, , Spain

Site Status

"Hospital Universitario Ramón y Cajal Servicio de Oncologia Médica"

Madrid, , Spain

Site Status

"HOSPITAL 12 DE OCTUBRE Servicio Oncología Médica"

Madrid, , Spain

Site Status

"Hospital Universitario Marqués de Valdecilla oncología medica"

Santander, , Spain

Site Status

H.VIRGEN DEL ROCIO Servicio de Oncología Médica

Seville, , Spain

Site Status

H. GENERAL DE VALENCIA Servicio de Oncología Médica

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet Edif. de maternidad planta 8. Servicio de Oncología Médical

Zaragoza, , Spain

Site Status

Kyiv City Clinical Oncological Centre

Kiev, Ukrain, Ukraine

Site Status

Cherkasy Regional Oncological Dispensary Regional Clinical Oncological Centre

Cherkassy, , Ukraine

Site Status

"MI ""Dnipropetrovsk City Multi-field Clinical Hospital #4"" Department of Oncology"

Dnipro, , Ukraine

Site Status

LLC Ukrainian Center of Tomotherapy "Tomoclinic", Chemoteraphy Department

Kropyvnytskyi, , Ukraine

Site Status

National Institute of Cancer Abdominal Oncology Department

Kyiv, , Ukraine

Site Status

Medical Center n.a. Acad. Spizhenko "Syber Clinic Spizhenko"" Department of Oncology

Kyiv, , Ukraine

Site Status

"Clinical and diagnostic Centre of Medics-rey Inter. Group LLC Hospital of Israeli Oncology "LISOD"

Kyiv, , Ukraine

Site Status

Podillia Regional Oncology Centre Chemotherapy Department

Vinnitsya, , Ukraine

Site Status

Countries

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United States Austria Belgium Brazil Denmark France Germany Hungary Italy Poland Puerto Rico Russia Spain Ukraine

References

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Prager GW, Taieb J, Fakih M, Ciardiello F, Van Cutsem E, Elez E, Cruz FM, Wyrwicz L, Stroyakovskiy D, Papai Z, Poureau PG, Liposits G, Cremolini C, Bondarenko I, Modest DP, Benhadji KA, Amellal N, Leger C, Vidot L, Tabernero J; SUNLIGHT Investigators. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer. N Engl J Med. 2023 May 4;388(18):1657-1667. doi: 10.1056/NEJMoa2214963.

Reference Type RESULT
PMID: 37133585 (View on PubMed)

Prager GW, Taieb J, Fakih M, Ciardiello F, Van Cutsem E, Elez E, Wyrwicz L, Stroyakovskiy D, Liposits G, Bondarenko I, Modest DP, Amellal N, Tabernero J; SUNLIGHT Investigators. Plain language summary of SUNLIGHT: trifluridine/tipiracil and bevacizumab for refractory metastatic colorectal cancer. Future Oncol. 2024;20(36):2823-2832. doi: 10.1080/14796694.2024.2366100. Epub 2024 Jul 2.

Reference Type DERIVED
PMID: 38953855 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2020-001976-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL3-95005-007

Identifier Type: -

Identifier Source: org_study_id

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