Last reviewed · How we verify

NCT04737187: SUNLIGHT

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

Completed Phase 3 Results posted Last updated 24 September 2024
What this trial tests

Phase 3 trial testing Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in 492 participants. Completed in 12 September 2023.

Timeline
25 November 2020
Primary endpoint
19 July 2022
12 September 2023

Quick facts

Lead sponsorTaiho Oncology, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment492
Start date25 November 2020
Primary completion19 July 2022
Estimated completion12 September 2023
Sites99 locations across Denmark, France, Italy, Russia, Ukraine, Belgium, Austria, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Taiho Oncology, Inc. — full company profile →

Who can join

18 and older, any sex, with Refractory Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Survival (OS) Primary · From date of randomization to the death due to any cause or cut-off 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab10.789.36 – 11.83
Trifluridine/Tipiracil7.466.34 – 8.57
Survival Probability at 6 Months Primary · 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.770.72 – 0.82
Trifluridine/Tipiracil0.610.55 – 0.67
Survival Probability at 12 Months Primary · 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.430.36 – 0.49
Trifluridine/Tipiracil0.300.24 – 0.36
Survival Probability at 18 Months Primary · 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.280.19 – 0.37
Trifluridine/Tipiracil0.150.09 – 0.22
Progression Free Survival (PFS) Secondary · 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab5.554.50 – 5.88
Trifluridine/Tipiracil2.402.07 – 3.22
Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months Secondary · 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.

At 3 Months
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.730.67 – 0.78
Trifluridine/Tipiracil0.450.39 – 0.51
At 6 Months
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.430.37 – 0.49
Trifluridine/Tipiracil0.160.11 – 0.21
At 9 Months
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.280.22 – 0.34
Trifluridine/Tipiracil0.050.03 – 0.09
At 12 Months
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.160.12 – 0.21
Trifluridine/Tipiracil0.010.00 – 0.03
Overall Response Rate (ORR) Secondary · 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.

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab6.103.45 – 9.86
Trifluridine/Tipiracil1.220.25 – 3.52
Percentage of Participants With Disease Control Secondary · 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 suffi

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab69.5163.35 – 75.2
Trifluridine/Tipiracil41.8735.63 – 48.31
Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs) Secondary · From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 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 peri

TEAE
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab241
Trifluridine/Tipiracil241
TESAE
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab66
Trifluridine/Tipiracil79
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 Secondary · 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)

EORTC QLQ-C30: 30 item questionnaires with 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4-point Likert scales with responses from "not at all" to "very much" and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw sco

Physical functioning
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.978.15 – 11.83
Trifluridine/Tipiracil4.503.71 – 5.62
Role functioning
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.577.49 – 10.94
Trifluridine/Tipiracil4.403.78 – 5.06
Emotional functioning
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab9.958.51 – 12.12
Trifluridine/Tipiracil5.854.70 – 6.60
Cognitive functioning
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab9.368.34 – 12.25
Trifluridine/Tipiracil4.734.07 – 6.11
Social functioning
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.977.85 – 11.86
Trifluridine/Tipiracil4.934.14 – 5.88
Fatigue
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.216.11 – 9.95
Trifluridine/Tipiracil4.043.19 – 4.83
Nausea and vomiting
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab9.368.51 – 11.86
Trifluridine/Tipiracil5.064.27 – 6.31
Pain
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.576.96 – 10.41
Trifluridine/Tipiracil4.343.29 – 5.16
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 Secondary · 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)

EORTC QLQ-C30: 30 item questionnaires composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/QOL subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4-point Likert scales with responses from "not at all" to "very much" and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to line

GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab8.547.49 – 10.94
Trifluridine/Tipiracil4.704.01 – 5.78
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 Secondary · 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

The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health utility and consist in 2 sections a descriptive system comprising 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and Visual Analog Scale (VAS). Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better hea

Cycle 1
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab0.004± 0.125
Trifluridine/Tipiracil0.001± 0.163
Cycle 2
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.003± 0.114
Trifluridine/Tipiracil-0.030± 0.153
Cycle 3
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.014± 0.107
Trifluridine/Tipiracil0.002± 0.188
Cycle 4
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.016± 0.111
Trifluridine/Tipiracil-0.014± 0.209
Cycle 5
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.003± 0.101
Trifluridine/Tipiracil0.004± 0.120
Cycle 6
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.010± 0.112
Trifluridine/Tipiracil-0.003± 0.094
Cycle 7
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.007± 0.078
Trifluridine/Tipiracil0.002± 0.105
Cycle 8
GroupValue95% CI
Trifluridine/Tipiracil + Bevacizumab-0.016± 0.097
Trifluridine/Tipiracil-0.028± 0.109

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Trifluridine/Tipiracil + Bevacizumab
Serious: 66/246 (27%)
Deaths: 208/246
Trifluridine/Tipiracil
Serious: 79/246 (32%)
Deaths: 224/246

Serious adverse events (136 terms)

ReactionSystemTrifluridine/Tipiracil + B…Trifluridine/Tipiracil
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnaemiaBlood and lymphatic system disorders
Intestinal obstructionGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
COVID-19Infections and infestations
JaundiceHepatobiliary disorders
Hepatic failureHepatobiliary disorders
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
Jaundice cholestaticHepatobiliary disorders
Metastases to meningesNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AstheniaGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
PyrexiaGeneral disorders
Blood bilirubin increasedInvestigations
Stoma site haemorrhageInjury, poisoning and procedural complications
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
Other adverse events (27 terms — click to expand)

ReactionSystemTrifluridine/Tipiracil + B…Trifluridine/Tipiracil
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
AstheniaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
Abdominal painGastrointestinal disorders
StomatitisGastrointestinal disorders
ConstipationGastrointestinal disorders
HypertensionVascular disorders
Platelet count decreasedInvestigations
COVID-19Infections and infestations
Weight decreasedInvestigations
Abdominal pain upperGastrointestinal disorders
HeadacheNervous system disorders
LeukopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
PyrexiaGeneral disorders
ProteinuriaRenal and urinary disorders

Most-reported serious reactions: Malignant neoplasm progression, Anaemia, Intestinal obstruction, Febrile neutropenia, COVID-19, Jaundice, Hepatic failure, Metastases to central nervous system.

Data from ClinicalTrials.gov NCT04737187 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.
    Prager GW, Taieb J, Fakih M, Ciardiello F, et al · · 2023 · cited 306× · PMID 37133585 · DOI 10.1056/nejmoa2214963
  2. Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives.
    Adebayo AS, Agbaje K, Adesina SK, Olajubutu O. · · 2023 · cited 65× · PMID 38004598 · DOI 10.3390/pharmaceutics15112620
  3. Advances in targeting tumor microenvironment for immunotherapy.
    Wang L, Zhang L, Zhang Z, Wu P, et al · · 2024 · cited 34× · PMID 39421736 · DOI 10.3389/fimmu.2024.1472772
  4. Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting.
    Martínez-Lago N, Chucla TC, De Castro BA, Ponte RV, et al · · 2022 · cited 13× · PMID 36028552 · DOI 10.1038/s41598-022-18871-9
  5. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study.
    Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, et al · · 2022 · cited 12× · PMID 35440667 · DOI 10.1038/s41416-022-01737-2
  6. Trifluridine/tipiracil with or without bevacizumab in metastatic colorectal cancer: results of a systematic review and meta-analysis.
    Yoshino T, Taieb J, Kuboki Y, Pfeiffer P, et al · · 2023 · cited 11× · PMID 36743525 · DOI 10.1177/17588359221146137
  7. A Comparison of Bevacizumab Plus TAS-102 and TAS-102 Monotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.
    Chen X, Qiu H, Chen Y, Wang M, et al · · 2021 · cited 6× · PMID 34868908 · DOI 10.3389/fonc.2021.690515
  8. Regorafenib is suitable for advanced colorectal cancer patients who have previously received trifluridine/tipiracil plus bevacizumab.
    Matsumoto T, Ikoma T, Yamamura S, Miura K, et al · · 2023 · cited 5× · PMID 36765099 · DOI 10.1038/s41598-023-29706-6

Verify or expand the search:

Other trials of Trifluridine/Tipiracil

Trials testing the same drug.

Other Taiho Oncology, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04737187.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing