ClinicalTrials.gov
History of Changes for Study: NCT04737187
Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients (SUNLIGHT)
Latest version (submitted December 5, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 2, 2021 None (earliest Version on record)
2 February 8, 2021 Contacts/Locations and Study Status
3 August 2, 2021 Study Status and Contacts/Locations
4 January 4, 2022 Contacts/Locations and Study Status
5 January 27, 2022 Contacts/Locations and Study Status
6 April 4, 2022 Recruitment Status, Contacts/Locations and Study Status
7 February 7, 2023 Study Status
8 March 15, 2023 Contacts/Locations and Study Status
9 March 16, 2023 Study Status
10 July 12, 2023 Study Status
11 October 17, 2023
Quality Control Review has not concluded Returned: November 10, 2023
Recruitment Status, Study Status, Outcome Measures, Study Design, Document Section, Adverse Events, Baseline Characteristics, Participant Flow, References, Contacts/Locations and Conditions
12 December 5, 2023 Study Status, Outcome Measures, Adverse Events, Arms and Interventions, Document Section, More Information, Baseline Characteristics, Participant Flow, Contacts/Locations and Study Identification
Comparison Format:
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Study NCT04737187
Submitted Date:  December 5, 2023 (v12)
Open or close this module Study Identification
Unique Protocol ID: CL3-95005-007
Brief Title: Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients (SUNLIGHT)
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)
Secondary IDs: 2020-001976-14 [EudraCT Number]
Open or close this module Study Status
Record Verification: December 2023
Overall Status: Completed
Study Start: November 25, 2020
Primary Completion: July 19, 2022 [Actual]
Study Completion: September 12, 2023 [Actual]
First Submitted: January 29, 2021
First Submitted that
Met QC Criteria:		 February 2, 2021
First Posted: February 3, 2021 [Actual]
Results First Submitted: October 17, 2023
Results First Submitted that
Met QC Criteria:		 December 5, 2023
Results First Posted: December 26, 2023 [Actual]
Certification/Extension
First Submitted:		 July 12, 2023
Certification/Extension
First Submitted that
Met QC Criteria:
Certification/Extension
First Posted:		 December 26, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:		 December 5, 2023
Last Update Posted: December 26, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Taiho Oncology, Inc.
Responsible Party: Sponsor
Collaborators: Institut de Recherches Internationales Servier
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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).
Open or close this module Conditions
Conditions: Refractory Metastatic Colorectal Cancer
Keywords: trifluridine/tipiracil/lonsurf
TAS102
bevacizumab
avastin
RAS status (wild type, mutant)
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 492 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 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.
 Drug: Trifluridine/Tipiracil
Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest
Other Names:
  • TAS102
  • S 95005
  • Lonsurf
Drug: Bevacizumab
administered every 2 weeks (Day 1 and Day 15)
Other Names:
  • Avastin
Active Comparator: 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.
 Drug: Trifluridine/Tipiracil
Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest
Other Names:
  • TAS102
  • S 95005
  • Lonsurf
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Overall Survival (OS)
[ Time Frame: From date of randomization to the death due to any cause or cut-ff date, whichever comes first (maximum duration: up to 20 months) ]

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.
2. Survival Probability at 6 Months
[ Time Frame: From date of randomization until 6 months post treatment ]

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.
3. Survival Probability at 12 Months
[ Time Frame: From date of randomization until 12 months post treatment ]

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.
4. Survival Probability at 18 Months
[ Time Frame: From date of randomization until 18 months post treatment ]

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.
Secondary Outcome Measures:
1. Progression Free Survival (PFS)
[ Time Frame: 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) ]

PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
2. Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months
[ Time Frame: From randomization until 3, 6, 9, and 12 months post treatment ]

PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method. In this outcome measure, data of PFS at 3 months was reported.
3. Overall Response Rate (ORR)
[ Time Frame: 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) ]

Objective response was defined as percentage of participants who achieved complete response (CR) or partial response (PR) according to the RECIST version 1.1 and using investigator's tumour assessment. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
4. Percentage of Participants With Disease Control
[ Time Frame: 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) ]

Disease control is defined as percentage of participants who achieved CR or PR, or stable disease (SD) as per RECIST 1.1 and using investigator's tumour assessment from the date of randomization to until disease progression or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
5. Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
[ Time Frame: From Baseline up to 30 days after the last dose of study treatments (i.e., up to 19.5 months) ]

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (time from the first dose of study treatment up to 30 days after the last dose of study treatment). TEAEs included both SAEs and non-SAEs.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Study Officials: Josep Tabernero, Prof
Principal Investigator
Vall d'Hebron Institute of Oncology
Locations: United States, Arizona
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
United States, California
City of Hope
Duarte, California, United States, 91010
City of Hope - South Pasedena
South Pasadena, California, United States, 91030
City of Hope - Upland
Upland, California, United States, 91786
United States, Florida
Mayo Clinic - FL
Jacksonville, Florida, United States, 32224
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Comprehensive Hematology Oncology
Saint Petersburg, Florida, United States, 33709
United States, Illinois
DuPage Medical Group - Joliet Oncology-Hematology Associates
Joliet, Illinois, United States, 60435
United States, Indiana
Investigative Clinical Research of Indiana LLC
Noblesville, Indiana, United States, 46062
United States, Nebraska
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68130
United States, New York
Mayo Clinic - Rochester
Rochester, New York, United States, 55905
United States, Texas
Renovatio Clinical - El Paso
El Paso, Texas, United States, 79915
Austria
"Medizinische Universität Graz "
Graz, Austria, 8036
"Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V"
Innsbruck, Austria, 6020
"Ordensklinikum Linz Barmherzige Schwestern Interne I"
Linz, Austria, 4010
"Landeskrankenhaus Feldkirch Interne E"
Rankweil, Austria, 6830
"Landeskrankenhaus (SALK) Universitätsklinik für Innere Medizin III (SALK)"
Salzburg, Austria, 5020
"Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie"
Wien, Austria, 1090
"Landesklinikum Wiener Neustadt "
Wiener Neustadt, Austria, 2700
Belgium
"OLV Ziekenhuis Oncology"
Aalst, Belgium, 9300
"Universitair Ziekenhuis Antwerpen Oncologie"
Edegem, Belgium, 2650
"UZ Leuven Campus Gasthuisberg Digestieve Oncologie"
Leuven, Belgium, 3000
"CHC Montlégia Oncologie"
Liege, Belgium, 4000
"AZ NIKOLAAS Oncology"
Sint Niklaas, Belgium, 9100
Brazil
"Hospital do Câncer de Barretos - Fundação Pio XII Unidade de Pesquisa Clínica"
Barretos, Brazil, 14784-400
"Hospital de Base Centro Integrado de Pesquisa"
Sao Jose Do Rio Preto, Brazil, 15090-000
"ICESP - Instituto do Câncer do Estado de São Paulo Centro Integrado de Pesquisa"
Sao Paulo, Brazil, 01246-000
Hospital A C Camargo Unidade de Pesquisa Clinica Rua Antonio Prudente
Sao Paulo, Brazil, 01509-900
Hospital Albert Einstein Instituto de Ensino e Pesquisa Av Albert Einstein
Sao Paulo, Brazil, 05652- 900
Hospital Sao Camilo Nucleo de Pesquisa Av Alcantara Machado
São Paulo, Brazil, 03102-002
Denmark
"Aalborg Universitetshospital, Syd Onkologisk Afdeling"
Aalborg, Denmark, 9000
Rigshospitalet Dpt of Oncology
Copenhagen, Denmark, 2100
"Regionshospitalet Herning, Hospitalsenheden Vest Onkologisk Afdeling"
Herning, Denmark, 7400
"Odense Universitetshospital Department of Oncology"
Odense, Denmark, 5000
France
"CHU Jean Minjoz Service d'oncologie médicale"
Besancon, France, 25030
"CHU Morvan Institut de Cancérologie et d'Hématologie"
Brest, France, 29200
"Centre de lutte contre le cancer Francois Baclesse UCP Digestif"
Caen, France, 14076
Hôpital Saint-Antoine Service d'Oncologie Médicale
Paris, France, 75012
"Hôpital Européen Georges Pompidou Oncologie Hépatogastroenterologie-oncologie digestive"
Paris, France, 75015
CHU de Poitiers Pole Régional de Cancérologie
Poitiers, France, 86021
Germany
Onkologische Schwerpunktpraxis Kurfuerstendamm
Berlin, Germany, 10707
Charite Universitätsmedizin Medizinische Klinik m.S. Haemat., Onko., Tumorimmunologie
Berlin, Germany, 13353
Lübecker Onkologische Schwerpunktpraxis im Hochschulstadttei
Luebeck, Germany, 23562
Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III
Muenchen, Germany, 81377
Hungary
Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly
Budapest, Hungary, 1062
Szent Imre Egyetemi Oktatokorhaz Klinikai Onkologiai Osztaly
Budapest, Hungary, 1115
Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Onkologiai Intezet
Debrecen, Hungary, 4032
Petz Aladar Megyei Oktato Korhaz Onkoradiologiai Osztaly
Győr, Hungary, 9024
Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
Kecskemét, Hungary, 6000
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kp. Onkoterápiás Klinika
Szeged, Hungary, 6720
JNSZ Megyei Hetenyi Geza Korhaz es Rendelointezet Megyei Onkologiai Centrum
Szolnok, Hungary, 5004
Markusovszky Egyetemi Oktatokorhaz Onkoradiologiai Osztaly
Szombathely, Hungary, 9700
Italy
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, 80131
Istituto Nazionale Tumori, I.R.C.C.S "Fondazione G Pascale" Struttura Complessa di Oncologia Medica Addominale
Napoli, Italy, 80131
Istituto Oncologico Veneto IOV - IRCCS Unita Operativa Complessa Oncologia Medica 1 Via Gattamelata 64
Padova, Italy, 35128
A.O.U. Pisana-Ospedale Santa Chiara U.O. di Oncologia Medica 2
Pisa, Italy, 56126
Ospedale San Carlo U.O. Oncologia Medica Via Potito Petrone, Ctr Macchia Romana
Potenza, Italy, 85100
Arcispedale Santa Maria Nuova Unità di Oncologia
Reggio Emilia, Italy, 42123
Istituto Clinico Humanita IRCCS Dipartimento di Oncologia Medica ed Ematologia Via Manzoni,
Rozzano (MI), Italy, 20089
IRCSS Casa Sollievo della Sofferenza Dipartimento Onco-Ematologia Vale Cappuccini 1
San Giovanni Rotondo, Italy, 71013
Italy, Italiy
Azienda Policlinico Universitaria - Presidio Monserrato Oncologia Medica Strada Statale 554 Sestu-Monserrato
Cagliari, Italiy, Italy, 9100
Poland
Przychodnia Lekarska "KOMED"
Konin, Poland, 62-500
SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii
Krakow, Poland, 31-531
Opolskie Centrum Onkologii im. Tadeusza Koszarowskiego Oddzial Onkologii Klinicznej
Opole, Poland, 45-061
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.
Słupsk, Poland, 76-200
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Klinika Onkologii i Radioterapii
Warszawa, Poland, 02-034
Wojskowy Instytut Medyczny Klinika Onkologii
Warszawa, Poland, 04-141
Centralny Szpital Kliniczny MSWiA Oddział Radioterapii i Onkologii
Warzszawa, Poland, 02-507
Puerto Rico
Pan American Center for Oncology Trials, LLC
Río Piedras, Puerto Rico, 00935
Russian Federation
Arkhangelsk Clinical Oncology Dispensary chemotherapy department
Arkhangelsk, Russian Federation, 163045
Clinical Oncology Dispensary No.1 Chemotherapy Department
Krasnodar, Russian Federation, 350040
Russian Cancer Research Center n.a. NN Blokhin Clinical Pharmacology and Chemotherapy
Moscow, Russian Federation, 115478
University Headache Clinic Outpatient oncology clinic
Moscow, Russian Federation, 121467
Moscow City Oncology Hospital # 62 chemotherapy department
Moscow Region, Russian Federation, 143423
Omsk Clinical Oncologic Dispensary Chemotherapy
Omsk, Russian Federation, 644046
National Medical Research Center of Oncology N.N. Petrova
Saint-petersburg, Russian Federation, 197758
Multidisciplinary clinic "Reaviz
Samara, Russian Federation, 443011
Oncology dispensary No.2 Oncology department
Sochi, Russian Federation, 354057
Scientific Centre for Specialized Medical Care (oncological) Chemotherapy
St Petersburg, Russian Federation, 115478
Saint Petersburg City Oncology Clilnic
St Petersburg, Russian Federation, 198255
SBIH of YR "Clinical oncology hospital chemotherapy department"
Yaroslavl, Russian Federation, 150054
Spain
"H. Valle de Hebrón Servicio de Oncología - (VHIR)"
Barcelona, Spain, 08035
"Hospital de la Santa Creu I Sant Pau Oncología Medica"
Barcelona, Spain, 08041
"Hospital Uni. Reina Sofía - Hospital Provincial Departamento de Oncología Médica"
Cordoba, Spain, 14004
"INSTITUTO CATALAN DE ONCOLOGÍA - ICO Oncología Médica"
Hospitalet de Llobregat, Spain, 08908
"Hospital Universitario Ramón y Cajal Servicio de Oncologia Médica"
Madrid, Spain, 28034
"HOSPITAL 12 DE OCTUBRE Servicio Oncología Médica"
Madrid, Spain, 28041
"Hospital Universitario Marqués de Valdecilla oncología medica"
Santander, Spain, 39008
H.VIRGEN DEL ROCIO Servicio de Oncología Médica
Sevilla, Spain, 41013
H. GENERAL DE VALENCIA Servicio de Oncología Médica
Valencia, Spain, 46014
Hospital Universitario Miguel Servet Edif. de maternidad planta 8. Servicio de Oncología Médical
Zaragoza, Spain, 50009
Ukraine
Cherkasy Regional Oncological Dispensary Regional Clinical Oncological Centre
Cherkassy, Ukraine, 18009
"MI ""Dnipropetrovsk City Multi-field Clinical Hospital #4"" Department of Oncology"
Dnipro, Ukraine, 49102
LLC Ukrainian Center of Tomotherapy "Tomoclinic", Chemoteraphy Department
Kropyvnytskyi, Ukraine, 25011
National Institute of Cancer Abdominal Oncology Department
Kyiv, Ukraine, 03022
Medical Center n.a. Acad. Spizhenko "Syber Clinic Spizhenko"" Department of Oncology
Kyiv, Ukraine, 08112
"Clinical and diagnostic Centre of Medics-rey Inter. Group LLC Hospital of Israeli Oncology "LISOD"
Kyiv, Ukraine, 08720
Podillia Regional Oncology Centre Chemotherapy Department
Vinnitsya, Ukraine, 21029
Ukraine, Ukrain
Kyiv City Clinical Oncological Centre
Kiev, Ukrain, Ukraine, 03115
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations: [Study Results] 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. PubMed 37133585
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: December 30, 2020
Uploaded: 10/16/2023 10:17
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: August 2, 2022
Uploaded: 10/16/2023 10:18
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details The study was conducted at 99 active sites in 13 countries. A total of 659 participants were screened, of which 492 participants were randomized and treated.
Pre-assignment Details Participants were randomized to 2 treatment arms in 1:1 ratio by interactive web response system stratified by geographic region (North America, European Union, Rest of the World), time since first metastasis diagnosis (less than [<] 18 months, greater than or equal to [>=] 18 months) and rat sarcoma virus (RAS) status (wild-type, mutant). Data reported based on primary completion date, i.e., 19 July 2022.
 
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Trifluridine/Tipiracil
Arm/Group Description 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 and 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. 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.
Period Title: Overall Study
Started 246 246
Completed 0 0
Not Completed 246 246
Reason Not Completed
Continuing the study on treatment 32 4
Radiological Progressive Disease 145 146
Clinical Progressive Disease 20 20
Radiological And Clinical Progressive Disease 26 52
Adverse Event 16 16
Physician Decision 2 0
Withdrawal by Subject 5 8
Open or close this module Baseline Characteristics
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/TipiracilTotal
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.Total of all reporting groups
Overall Number of Baseline Participants 246 246 492
Baseline Analysis Population Description
Age, Continuous
Median (Full Range)
Unit of measure: years
Number Analyzed246 Participants246 Participants492 Participants
62.00(20.0 to 84.0)64.00(24.0 to 90.0)63.00(20.0 to 90.0)
Age, Customized
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed246 Participants246 Participants492 Participants
Adults (18-64 years)
146
59.35%
129
52.44%
275
55.89%
From 65-84 years
100
40.65%
116
47.15%
216
43.9%
85 years and over
0
0%
1
0.41%
1
0.2%
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed246 Participants246 Participants492 Participants
Female
124
50.41%
112
45.53%
236
47.97%
Male
122
49.59%
134
54.47%
256
52.03%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed246 Participants246 Participants492 Participants
American Indian or Alaska Native
1
0.41%
0
0%
1
0.2%
Asian
0
0%
1
0.41%
1
0.2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
4
1.63%
3
1.22%
7
1.42%
White
215
87.4%
220
89.43%
435
88.41%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
26
10.57%
22
8.94%
48
9.76%
Open or close this module Outcome Measures
1. Primary Outcome:
Title Overall Survival (OS)
Description Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.
Time Frame From date of randomization to the death due to any cause or cut-ff date, whichever comes first (maximum duration: up to 20 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Median (95% Confidence Interval)
Unit of Measure: months
10.78(9.36 to 11.83) 7.46(6.34 to 8.57)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionTrifluridine/Tipiracil + Bevacizumab, Trifluridine/Tipiracil
CommentsOverall Survival Median analysis: The primary estimand was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy).
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value< 0.001
CommentsStratified log-rank test, with a target p-value < 0.025 for level of significance.
MethodStratified log-rank test
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.61
Confidence Interval(2-sided) 95%
0.49 to 0.77
Estimation CommentsHazard ratio and 95% confidence interval was estimated with stratified Cox proportional hazard model.
2. Primary Outcome:
Title Survival Probability at 6 Months
Description Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.
Time Frame From date of randomization until 6 months post treatment
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: probability of participants
0.77(0.72 to 0.82) 0.61(0.55 to 0.67)
3. Primary Outcome:
Title Survival Probability at 12 Months
Description Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.
Time Frame From date of randomization until 12 months post treatment
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: probability of participants
0.43(0.36 to 0.49) 0.30(0.24 to 0.36)
4. Primary Outcome:
Title Survival Probability at 18 Months
Description Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.
Time Frame From date of randomization until 18 months post treatment
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: probability of participants
0.28(0.19 to 0.37) 0.15(0.09 to 0.22)
5. Secondary Outcome:
Title Progression Free Survival (PFS)
Description PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.
Time Frame 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)
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Median (95% Confidence Interval)
Unit of Measure: months
5.55(4.50 to 5.88) 2.40(2.07 to 3.22)
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionTrifluridine/Tipiracil + Bevacizumab, Trifluridine/Tipiracil
CommentsPFS Median analysis: A hierarchical testing method was used to control type I error and handle key secondary endpoint analysis. When the primary outcome measure significant testing was then performed sequentially on the key secondary outcome measure. statistically significant at 0.05 level.
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value< 0.001
CommentsStratified log-rank test, with a target p-value < 0.025 for level of significance.
MethodStratified log-rank test
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.44
Confidence Interval(2-sided) 95%
0.36 to 0.54
Estimation CommentsHazard ratio and 95% confidence interval was estimated with stratified Cox proportional hazard model.
6. Secondary Outcome:
Title Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months
Description PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method. In this outcome measure, data of PFS at 3 months was reported.
Time Frame From randomization until 3, 6, 9, and 12 months post treatment
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: probability of participants
At 3 Months
0.73(0.67 to 0.78) 0.45(0.39 to 0.51)
At 6 Months
0.43(0.37 to 0.49) 0.16(0.11 to 0.21)
At 9 Months
0.28(0.22 to 0.34) 0.05(0.03 to 0.09)
At 12 Months
0.16(0.12 to 0.21) 0.01(0.00 to 0.03)
7. Secondary Outcome:
Title Overall Response Rate (ORR)
Description Objective response was defined as percentage of participants who achieved complete response (CR) or partial response (PR) according to the RECIST version 1.1 and using investigator's tumour assessment. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.
Time Frame 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)
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.10(3.45 to 9.86) 1.22(0.25 to 3.52)
8. Secondary Outcome:
Title Percentage of Participants With Disease Control
Description Disease control is defined as percentage of participants who achieved CR or PR, or stable disease (SD) as per RECIST 1.1 and using investigator's tumour assessment from the date of randomization to until disease progression or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.
Time Frame 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)
Outcome Measure Data
Analysis Population Description
Analysis was performed on FAS population.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
69.51(63.35 to 75.2) 41.87(35.63 to 48.31)
9. Secondary Outcome:
Title Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs)
Description An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (time from the first dose of study treatment up to 30 days after the last dose of study treatment). TEAEs included both SAEs and non-SAEs.
Time Frame From Baseline up to 30 days after the last dose of study treatments (i.e., up to 19.5 months)
Outcome Measure Data
Analysis Population Description
Analysis was performed on safety set which included all participants who had taken at least one dose of investigational medicinal products and were analyzed according to the treatment they actually received.
 
Arm/Group TitleTrifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
Arm/Group DescriptionParticipants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.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.
Overall Number of Participants Analyzed246 246
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE
241
98%
241
98%
TESAE
61
24.8%
77
31.3%
Open or close this module Adverse Events
 
Time Frame From baseline up to the cut-off date (19 July 2022, i.e., up to 20 months)
Adverse Event Reporting Description Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received.
 
Arm/Group Title Trifluridine/Tipiracil + Bevacizumab Trifluridine/Tipiracil
Arm/Group Description Participants were administered 35 mg/m²/dose 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; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks. 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.
All-Cause Mortality
  Trifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
 Affected / At Risk (%)Affected / At Risk (%)
Total 148 / 246 (60.16%)183 / 246 (74.39%)
Serious Adverse Events
  Trifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
 Affected / At Risk (%)Affected / At Risk (%)
Total 61 / 246 (24.8%)77 / 246 (31.3%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy † A 0 / 246 (0%)1 / 246 (0.41%)
Anaemia † A 1 / 246 (0.41%)8 / 246 (3.25%)
Febrile neutropenia † A 1 / 246 (0.41%)6 / 246 (2.44%)
Iron deficiency anaemia † A 1 / 246 (0.41%)0 / 246 (0%)
Neutropenia † A 2 / 246 (0.81%)1 / 246 (0.41%)
Cardiac disorders
Angina pectoris † A 1 / 246 (0.41%)1 / 246 (0.41%)
Atrial fibrillation † A 1 / 246 (0.41%)1 / 246 (0.41%)
Cardiac failure † A 1 / 246 (0.41%)1 / 246 (0.41%)
Cardiac failure acute † A 0 / 246 (0%)1 / 246 (0.41%)
Cardiac failure congestive † A 1 / 246 (0.41%)0 / 246 (0%)
Pericardial effusion † A 1 / 246 (0.41%)0 / 246 (0%)
Pericarditis † A 1 / 246 (0.41%)0 / 246 (0%)
Congenital, familial and genetic disorders
Phimosis † A 1 / 246 (0.41%)0 / 246 (0%)
Eye disorders
Glaucoma † A 1 / 246 (0.41%)0 / 246 (0%)
Gastrointestinal disorders
Abdominal hernia † A 1 / 246 (0.41%)0 / 246 (0%)
Abdominal pain † A 2 / 246 (0.81%)1 / 246 (0.41%)
Abdominal pain upper † A 1 / 246 (0.41%)2 / 246 (0.81%)
Abdominal tenderness † A 1 / 246 (0.41%)0 / 246 (0%)
Anal fistula † A 1 / 246 (0.41%)0 / 246 (0%)
Ascites † A 1 / 246 (0.41%)2 / 246 (0.81%)
Colitis † A 1 / 246 (0.41%)0 / 246 (0%)
Constipation † A 0 / 246 (0%)2 / 246 (0.81%)
Diarrhoea † A 0 / 246 (0%)3 / 246 (1.22%)
Gastritis haemorrhagic † A 0 / 246 (0%)1 / 246 (0.41%)
Gastrointestinal fistula † A 1 / 246 (0.41%)0 / 246 (0%)
Gastrointestinal haemorrhage † A 0 / 246 (0%)1 / 246 (0.41%)
Gastrointestinal ischaemia † A 0 / 246 (0%)1 / 246 (0.41%)
Gastrointestinal perforation † A 1 / 246 (0.41%)0 / 246 (0%)
Ileus † A 1 / 246 (0.41%)1 / 246 (0.41%)
Intestinal obstruction † A 7 / 246 (2.85%)5 / 246 (2.03%)
Intestinal perforation † A 1 / 246 (0.41%)0 / 246 (0%)
Large intestinal obstruction † A 2 / 246 (0.81%)0 / 246 (0%)
Large intestinal stenosis † A 1 / 246 (0.41%)0 / 246 (0%)
Nausea † A 2 / 246 (0.81%)0 / 246 (0%)
Neutropenic colitis † A 1 / 246 (0.41%)0 / 246 (0%)
Small intestinal stenosis † A 0 / 246 (0%)1 / 246 (0.41%)
Subileus † A 0 / 246 (0%)1 / 246 (0.41%)
Vomiting † A 2 / 246 (0.81%)2 / 246 (0.81%)
General disorders
Asthenia † A 1 / 246 (0.41%)0 / 246 (0%)
Death † A 0 / 246 (0%)1 / 246 (0.41%)
Fatigue † A 0 / 246 (0%)3 / 246 (1.22%)
General physical health deterioration † A 0 / 246 (0%)1 / 246 (0.41%)
Malaise † A 0 / 246 (0%)1 / 246 (0.41%)
Multiple organ dysfunction syndrome † A 0 / 246 (0%)2 / 246 (0.81%)
Pain † A 1 / 246 (0.41%)0 / 246 (0%)
Pyrexia † A 0 / 246 (0%)2 / 246 (0.81%)
Hepatobiliary disorders
Bile duct stenosis † A 2 / 246 (0.81%)0 / 246 (0%)
Bile duct stone † A 1 / 246 (0.41%)0 / 246 (0%)
Biliary dilatation † A 2 / 246 (0.81%)0 / 246 (0%)
Cholangitis † A 2 / 246 (0.81%)1 / 246 (0.41%)
Cholecystitis acute † A 1 / 246 (0.41%)0 / 246 (0%)
Cholestasis † A 0 / 246 (0%)1 / 246 (0.41%)
Hepatic failure † A 0 / 246 (0%)5 / 246 (2.03%)
Hepatomegaly † A 0 / 246 (0%)1 / 246 (0.41%)
Hyperbilirubinaemia † A 2 / 246 (0.81%)0 / 246 (0%)
Jaundice † A 2 / 246 (0.81%)5 / 246 (2.03%)
Jaundice cholestatic † A 3 / 246 (1.22%)0 / 246 (0%)
Immune system disorders
Anaphylactic reaction † A 1 / 246 (0.41%)0 / 246 (0%)
Infections and infestations
Abdominal infection † A 0 / 246 (0%)1 / 246 (0.41%)
Abdominal sepsis † A 1 / 246 (0.41%)0 / 246 (0%)
Bacterial prostatitis † A 0 / 246 (0%)1 / 246 (0.41%)
Bacterial pyelonephritis † A 0 / 246 (0%)2 / 246 (0.81%)
Bronchitis † A 0 / 246 (0%)1 / 246 (0.41%)
COVID-19 † A 5 / 246 (2.03%)6 / 246 (2.44%)
COVID-19 pneumonia † A 1 / 246 (0.41%)0 / 246 (0%)
Infection † A 0 / 246 (0%)2 / 246 (0.81%)
Intestinal sepsis † A 1 / 246 (0.41%)0 / 246 (0%)
Klebsiella sepsis † A 0 / 246 (0%)1 / 246 (0.41%)
Nasopharyngitis † A 0 / 246 (0%)1 / 246 (0.41%)
Paracancerous pneumonia † A 1 / 246 (0.41%)0 / 246 (0%)
Pelvic abscess † A 0 / 246 (0%)1 / 246 (0.41%)
Peritonitis † A 1 / 246 (0.41%)0 / 246 (0%)
Pneumonia † A 1 / 246 (0.41%)2 / 246 (0.81%)
Pneumonia streptococcal † A 1 / 246 (0.41%)0 / 246 (0%)
Postoperative abscess † A 1 / 246 (0.41%)0 / 246 (0%)
Pyelonephritis † A 1 / 246 (0.41%)0 / 246 (0%)
Sepsis † A 0 / 246 (0%)1 / 246 (0.41%)
Septic shock † A 2 / 246 (0.81%)0 / 246 (0%)
Staphylococcal sepsis † A 1 / 246 (0.41%)0 / 246 (0%)
Urinary tract infection † A 0 / 246 (0%)1 / 246 (0.41%)
Urinary tract infection bacterial † A 1 / 246 (0.41%)0 / 246 (0%)
Urinary tract infection pseudomonal † A 1 / 246 (0.41%)0 / 246 (0%)
Urosepsis † A 0 / 246 (0%)1 / 246 (0.41%)
Vascular device infection † A 1 / 246 (0.41%)1 / 246 (0.41%)
Injury, poisoning and procedural complications
Gastrointestinal stoma complication † A 0 / 246 (0%)1 / 246 (0.41%)
Humerus fracture † A 1 / 246 (0.41%)0 / 246 (0%)
Spinal compression fracture † A 1 / 246 (0.41%)1 / 246 (0.41%)
Stoma site haemorrhage † A 2 / 246 (0.81%)0 / 246 (0%)
Investigations
Blood alkaline phosphatase increased † A 1 / 246 (0.41%)0 / 246 (0%)
Blood bilirubin increased † A 2 / 246 (0.81%)0 / 246 (0%)
C-reactive protein increased † A 0 / 246 (0%)1 / 246 (0.41%)
Gastrointestinal stoma output decreased † A 0 / 246 (0%)1 / 246 (0.41%)
Neutrophil count increased † A 0 / 246 (0%)1 / 246 (0.41%)
Metabolism and nutrition disorders
Cachexia † A 0 / 246 (0%)2 / 246 (0.81%)
Dehydration † A 1 / 246 (0.41%)2 / 246 (0.81%)
Hypernatraemia † A 1 / 246 (0.41%)0 / 246 (0%)
Hyponatraemia † A 0 / 246 (0%)1 / 246 (0.41%)
Musculoskeletal and connective tissue disorders
Arthralgia † A 0 / 246 (0%)1 / 246 (0.41%)
Muscular weakness † A 1 / 246 (0.41%)0 / 246 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † A 0 / 246 (0%)1 / 246 (0.41%)
Malignant neoplasm progression † A 6 / 246 (2.44%)11 / 246 (4.47%)
Malignant pleural effusion † A 0 / 246 (0%)1 / 246 (0.41%)
Metastases to central nervous system † A 0 / 246 (0%)4 / 246 (1.63%)
Metastases to meninges † A 2 / 246 (0.81%)0 / 246 (0%)
Metastases to ovary † A 0 / 246 (0%)1 / 246 (0.41%)
Metastases to spine † A 1 / 246 (0.41%)0 / 246 (0%)
Tumour pain † A 1 / 246 (0.41%)0 / 246 (0%)
Nervous system disorders
Balance disorder † A 1 / 246 (0.41%)0 / 246 (0%)
Cerebrovascular accident † A 0 / 246 (0%)1 / 246 (0.41%)
Diplegia † A 0 / 246 (0%)1 / 246 (0.41%)
Dizziness † A 1 / 246 (0.41%)0 / 246 (0%)
Haemorrhagic stroke † A 1 / 246 (0.41%)0 / 246 (0%)
Headache † A 1 / 246 (0.41%)0 / 246 (0%)
Hepatic encephalopathy † A 0 / 246 (0%)1 / 246 (0.41%)
Hypoaesthesia † A 1 / 246 (0.41%)0 / 246 (0%)
Psychiatric disorders
Confusional state † A 0 / 246 (0%)1 / 246 (0.41%)
Psychomotor retardation † A 0 / 246 (0%)1 / 246 (0.41%)
Renal and urinary disorders
Acute kidney injury † A 2 / 246 (0.81%)2 / 246 (0.81%)
Haematuria † A 0 / 246 (0%)1 / 246 (0.41%)
Prerenal failure † A 0 / 246 (0%)1 / 246 (0.41%)
Pyelocaliectasis † A 1 / 246 (0.41%)0 / 246 (0%)
Urinary incontinence † A 1 / 246 (0.41%)0 / 246 (0%)
Reproductive system and breast disorders
Prostatitis † A 1 / 246 (0.41%)0 / 246 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † A 0 / 246 (0%)1 / 246 (0.41%)
Dyspnoea † A 1 / 246 (0.41%)0 / 246 (0%)
Dyspnoea at rest † A 0 / 246 (0%)1 / 246 (0.41%)
Epistaxis † A 1 / 246 (0.41%)0 / 246 (0%)
Pleural effusion † A 0 / 246 (0%)1 / 246 (0.41%)
Pulmonary embolism † A 1 / 246 (0.41%)4 / 246 (1.63%)
Respiratory failure † A 0 / 246 (0%)1 / 246 (0.41%)
Vascular disorders
Deep vein thrombosis † A 1 / 246 (0.41%)1 / 246 (0.41%)
Hypertension † A 1 / 246 (0.41%)0 / 246 (0%)
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA (25.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Trifluridine/Tipiracil + BevacizumabTrifluridine/Tipiracil
 Affected / At Risk (%)Affected / At Risk (%)
Total 238 / 246 (96.75%)237 / 246 (96.34%)
Blood and lymphatic system disorders
Anaemia † A 70 / 246 (28.46%)71 / 246 (28.86%)
Leukopenia † A 16 / 246 (6.5%)21 / 246 (8.54%)
Neutropenia † A 153 / 246 (62.2%)126 / 246 (51.22%)
Thrombocytopenia † A 42 / 246 (17.07%)28 / 246 (11.38%)
Gastrointestinal disorders
Abdominal pain † A 27 / 246 (10.98%)26 / 246 (10.57%)
Abdominal pain upper † A 21 / 246 (8.54%)8 / 246 (3.25%)
Constipation † A 27 / 246 (10.98%)27 / 246 (10.98%)
Diarrhoea † A 51 / 246 (20.73%)46 / 246 (18.7%)
Nausea † A 90 / 246 (36.59%)67 / 246 (27.24%)
Stomatitis † A 27 / 246 (10.98%)9 / 246 (3.66%)
Vomiting † A 45 / 246 (18.29%)35 / 246 (14.23%)
General disorders
Asthenia † A 59 / 246 (23.98%)55 / 246 (22.36%)
Fatigue † A 53 / 246 (21.54%)37 / 246 (15.04%)
Pyrexia † A 12 / 246 (4.88%)14 / 246 (5.69%)
Investigations
Alanine aminotransferase increased † A 21 / 246 (8.54%)14 / 246 (5.69%)
Aspartate aminotransferase increased † A 21 / 246 (8.54%)14 / 246 (5.69%)
Blood bilirubin increased † A 12 / 246 (4.88%)14 / 246 (5.69%)
Neutrophil count decreased † A 34 / 246 (13.82%)17 / 246 (6.91%)
Platelet count decreased † A 22 / 246 (8.94%)5 / 246 (2.03%)
Weight decreased † A 20 / 246 (8.13%)12 / 246 (4.88%)
Metabolism and nutrition disorders
Decreased appetite † A 50 / 246 (20.33%)38 / 246 (15.45%)
Musculoskeletal and connective tissue disorders
Arthralgia † A 17 / 246 (6.91%)5 / 246 (2.03%)
Back pain † A 16 / 246 (6.5%)13 / 246 (5.28%)
Nervous system disorders
Headache † A 19 / 246 (7.72%)9 / 246 (3.66%)
Renal and urinary disorders
Proteinuria † A 15 / 246 (6.1%)3 / 246 (1.22%)
Vascular disorders
Hypertension † A 24 / 246 (9.76%)5 / 246 (2.03%)
†Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA (25.0)
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:
Name/Official Title:
 Taiho
Organization:
 Taiho Oncology, Inc.
Phone:
 1-609-250-7336
Email:
 clinicaltrialinfo@taihooncology.com
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