Clinical trial NCT04737187: Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients
Official title: An Open-label, Randomized, Phase III Study Comparing Trifluridine/Tipiracil in Combination With Bevacizumab to Trifluridine/Tipiracil Monotherapy in Patients With Refractory Metastatic Colorectal Cancer (SUNLIGHT Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Refractory Metastatic Colorectal Cancer
Keywords: trifluridine/tipiracil/lonsurf
TAS102
bevacizumab
avastin
RAS status (wild type, mutant)
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Institut de Recherches Internationales Servier
First posted: 2021-02-03
Enrollment: 492
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: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)
measure: Survival Probability at 6 Months
timeFrame: From date of randomization until 6 months post treatment
measure: Survival Probability at 12 Months
timeFrame: From date of randomization until 12 months post treatment
measure: Survival Probability at 18 Months
timeFrame: From date of randomization until 18 months post treatment
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization to the date of radiological tumour progression or death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)
measure: Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months
timeFrame: From randomization until 3, 6, 9, and 12 months post treatment
measure: Overall Response Rate (ORR)
timeFrame: From the date of randomization to the date of documentation of progression or death due to any cause or data cut-off, whichever occurred first (i.e., up to 20 months)
measure: Percentage of Participants With Disease Control
timeFrame: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months)
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis
timeFrame: Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)
measure: European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in the Global Health Status Score - Kaplan-Meier Analysis
timeFrame: Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)
measure: Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints
timeFrame: Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14
measure: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints
timeFrame: Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: South Pasadena
country: United States
facility: City of Hope - South Pasedena
state: California
city: Upland
country: United States
facility: City of Hope - Upland
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - FL
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology Oncology
state: Florida
city: Joliet
country: United States
facility: DuPage Medical Group - Joliet Oncology-Hematology Associates
state: Illinois
city: Noblesville
country: United States
facility: Investigative Clinical Research of Indiana LLC
state: Indiana
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: New York
city: El Paso
country: United States
facility: Renovatio Clinical - El Paso
state: Texas
city: Graz
country: Austria
facility: "Medizinische Universität Graz "
city: Innsbruck
country: Austria
facility: "Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V"
city: Linz
country: Austria
facility: "Ordensklinikum Linz Barmherzige Schwestern Interne I"
city: Rankweil
country: Austria
facility: "Landeskrankenhaus Feldkirch Interne E"
city: Salzburg
country: Austria
facility: "Landeskrankenhaus (SALK) Universitätsklinik für Innere Medizin III (SALK)"
city: Wiener Neustadt
country: Austria
facility: "Landesklinikum Wiener Neustadt "
city: Wien
country: Austria
facility: "Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie"
city: Aalst
country: Belgium
facility: "OLV Ziekenhuis Oncology"
city: Edegem
country: Belgium
facility: "Universitair Ziekenhuis Antwerpen Oncologie"
city: Leuven
country: Belgium
facility: "UZ Leuven Campus Gasthuisberg Digestieve Oncologie"
city: Liege
country: Belgium
facility: "CHC Montlégia Oncologie"
city: Sint Niklaas
country: Belgium
facility: "AZ NIKOLAAS Oncology"
city: Barretos
country: Brazil
facility: "Hospital do Câncer de Barretos - Fundação Pio XII Unidade de Pesquisa Clínica"
city: Sao Jose Do Rio Preto
country: Brazil
facility: "Hospital de Base Centro Integrado de Pesquisa"
city: Sao Paulo
country: Brazil
facility: "ICESP - Instituto do Câncer do Estado de São Paulo Centro Integrado de Pesquisa"
city: Sao Paulo
country: Brazil
facility: Hospital A C Camargo Unidade de Pesquisa Clinica Rua Antonio Prudente
city: Sao Paulo
country: Brazil
facility: Hospital Albert Einstein Instituto de Ensino e Pesquisa Av Albert Einstein
city: São Paulo
country: Brazil
facility: Hospital Sao Camilo Nucleo de Pesquisa Av Alcantara Machado
city: Aalborg
country: Denmark
facility: "Aalborg Universitetshospital, Syd Onkologisk Afdeling"
city: Copenhagen
country: Denmark
facility: Rigshospitalet Dpt of Oncology
city: Herning
country: Denmark
facility: "Regionshospitalet Herning, Hospitalsenheden Vest Onkologisk Afdeling"
city: Odense
country: Denmark
facility: "Odense Universitetshospital Department of Oncology"
city: Besancon
country: France
facility: "CHU Jean Minjoz Service d'oncologie médicale"
city: Brest
country: France
facility: "CHU Morvan Institut de Cancérologie et d'Hématologie"
city: Caen
country: France
facility: "Centre de lutte contre le cancer Francois Baclesse UCP Digestif"
city: Paris
country: France
facility: Hôpital Saint-Antoine Service d'Oncologie Médicale
city: Paris
country: France
facility: "Hôpital Européen Georges Pompidou Oncologie Hépatogastroenterologie-oncologie digestive"
city: Poitiers
country: France
facility: CHU de Poitiers Pole Régional de Cancérologie
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfuerstendamm
city: Berlin
country: Germany
facility: Charite Universitätsmedizin Medizinische Klinik m.S. Haemat., Onko., Tumorimmunologie
city: Luebeck
country: Germany
facility: Lübecker Onkologische Schwerpunktpraxis im Hochschulstadttei
city: Muenchen
country: Germany
facility: Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly
city: Budapest
country: Hungary
facility: Szent Imre Egyetemi Oktatokorhaz Klinikai Onkologiai Osztaly
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Onkologiai Intezet
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz Onkoradiologiai Osztaly
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kp. Onkoterápiás Klinika
city: Szolnok
country: Hungary
facility: JNSZ Megyei Hetenyi Geza Korhaz es Rendelointezet Megyei Onkologiai Centrum
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatokorhaz Onkoradiologiai Osztaly
city: Cagliari
country: Italy
facility: Azienda Policlinico Universitaria - Presidio Monserrato Oncologia Medica Strada Statale 554 Sestu-Monserrato
state: Italiy
city: Napoli
country: Italy
facility: 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 ,
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori, I.R.C.C.S "Fondazione G Pascale" Struttura Complessa di Oncologia Medica Addominale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IOV - IRCCS Unita Operativa Complessa Oncologia Medica 1 Via Gattamelata 64
city: Pisa
country: Italy
facility: A.O.U. Pisana-Ospedale Santa Chiara U.O. di Oncologia Medica 2
city: Potenza
country: Italy
facility: Ospedale San Carlo U.O. Oncologia Medica Via Potito Petrone, Ctr Macchia Romana
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova Unità di Oncologia
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanita IRCCS Dipartimento di Oncologia Medica ed Ematologia Via Manzoni,
city: San Giovanni Rotondo
country: Italy
facility: IRCSS Casa Sollievo della Sofferenza Dipartimento Onco-Ematologia Vale Cappuccini 1
city: Konin
country: Poland
facility: Przychodnia Lekarska "KOMED"
city: Krakow
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii
city: Opole
country: Poland
facility: Opolskie Centrum Onkologii im. Tadeusza Koszarowskiego Oddzial Onkologii Klinicznej
city: Słupsk
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Klinika Onkologii i Radioterapii
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny Klinika Onkologii
city: Warzszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA Oddział Radioterapii i Onkologii
city: Río Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Clinical Oncology Dispensary chemotherapy department
city: Krasnodar
country: Russian Federation
facility: Clinical Oncology Dispensary No.1 Chemotherapy Department
city: Moscow Region
country: Russian Federation
facility: Moscow City Oncology Hospital # 62 chemotherapy department
city: Moscow
country: Russian Federation
facility: Russian Cancer Research Center n.a. NN Blokhin Clinical Pharmacology and Chemotherapy
city: Moscow
country: Russian Federation
facility: University Headache Clinic Outpatient oncology clinic
city: Omsk
country: Russian Federation
facility: Omsk Clinical Oncologic Dispensary Chemotherapy
city: Saint-petersburg
country: Russian Federation
facility: National Medical Research Center of Oncology N.N. Petrova
city: Samara
country: Russian Federation
facility: Multidisciplinary clinic "Reaviz
city: Sochi
country: Russian Federation
facility: Oncology dispensary No.2 Oncology department
city: St Petersburg
country: Russian Federation
facility: Scientific Centre for Specialized Medical Care (oncological) Chemotherapy
city: St Petersburg
country: Russian Federation
facility: Saint Petersburg City Oncology Clilnic
city: Yaroslavl
country: Russian Federation
facility: SBIH of YR "Clinical oncology hospital chemotherapy department"
city: Barcelona
country: Spain
facility: "H. Valle de Hebrón Servicio de Oncología - (VHIR)"
city: Barcelona
country: Spain
facility: "Hospital de la Santa Creu I Sant Pau Oncología Medica"
city: Cordoba
country: Spain
facility: "Hospital Uni. Reina Sofía - Hospital Provincial Departamento de Oncología Médica"
city: Hospitalet de Llobregat
country: Spain
facility: "INSTITUTO CATALAN DE ONCOLOGÍA - ICO Oncología Médica"
city: Madrid
country: Spain
facility: "Hospital Universitario Ramón y Cajal Servicio de Oncologia Médica"
city: Madrid
country: Spain
facility: "HOSPITAL 12 DE OCTUBRE Servicio Oncología Médica"
city: Santander
country: Spain
facility: "Hospital Universitario Marqués de Valdecilla oncología medica"
city: Sevilla
country: Spain
facility: H.VIRGEN DEL ROCIO Servicio de Oncología Médica
city: Valencia
country: Spain
facility: H. GENERAL DE VALENCIA Servicio de Oncología Médica
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet Edif. de maternidad planta 8. Servicio de Oncología Médical
city: Kiev
country: Ukraine
facility: Kyiv City Clinical Oncological Centre
state: Ukrain
city: Cherkassy
country: Ukraine
facility: Cherkasy Regional Oncological Dispensary Regional Clinical Oncological Centre
city: Dnipro
country: Ukraine
facility: MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" Department of Oncology
city: Kropyvnytskyi
country: Ukraine
facility: LLC Ukrainian Center of Tomotherapy "Tomoclinic", Chemoteraphy Department
city: Kyiv
country: Ukraine
facility: National Institute of Cancer Abdominal Oncology Department
city: Kyiv
country: Ukraine
facility: Medical Center n.a. Acad. Spizhenko "Syber Clinic Spizhenko"" Department of Oncology
city: Kyiv
country: Ukraine
facility: "Clinical and diagnostic Centre of Medics-rey Inter. Group LLC Hospital of Israeli Oncology "LISOD"
city: Vinnitsya
country: Ukraine
facility: Podillia Regional Oncology Centre Chemotherapy Department
Study officials:
affiliation: Vall d'Hebron Institute of Oncology
name: Josep Tabernero, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.