Clinical Trials /

Phase III Study of Trifluridine/Tipiracil in Combination With Bevacizumab vs Trifluridine/Tipiracil Single Agent in Patients With Refractory Metastatic Colorectal Cancer

NCT04737187

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Study of Trifluridine/Tipiracil in Combination With Bevacizumab vs Trifluridine/Tipiracil Single Agent in Patients With Refractory Metastatic Colorectal Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: CL3-95005-007
  • SECONDARY ID: 2020-001976-14
  • NCT ID: NCT04737187

Conditions

  • Refractory Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
Trifluridine/TipiracilTAS102, S 95005, Lonsurftrifluridine/tipiracil in combination with bevacizumab
BevacizumabAvastintrifluridine/tipiracil in combination with bevacizumab

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
trifluridine/tipiracil in combination with bevacizumabExperimental
  • Trifluridine/Tipiracil
  • Bevacizumab
trifluridine/tipiracil monotherapyActive Comparator
  • Trifluridine/Tipiracil

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Approximately 12 months
Safety Issue:
Description:Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Approximately 12 months
Safety Issue:
Description:Progression-free survival defined as the time elapsed between the randomization and the date of radiologic tumour progression according to RECIST version 1.1 (Eisenhauer, 2009) by investigator's judgement or death from any cause, whichever comes first.
Measure:Overall response rate (ORR)
Time Frame:Approximately 12 months
Safety Issue:
Description:Overall response rate defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria and using investigator's tumor assessment
Measure:Disease control rate (DCR)
Time Frame:Approximately 12 months
Safety Issue:
Description:Disease control rate defined as the proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST version 1.1 criteria and using investigator's tumor assessment
Measure:Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs) for safety and tolerability assessment of study drug(s)
Time Frame:Approximately 12 months
Safety Issue:
Description:Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs)
Measure:Quality of life: EORTC QLQ-C30
Time Frame:Approximately 12 months
Safety Issue:
Description:Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module.
Measure:Quality of life: EQ-5D-5L
Time Frame:Approximately 12 months
Safety Issue:
Description:Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EQ-5D-5L) module.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Taiho Oncology, Inc.

Trial Keywords

  • trifluridine/tipiracil
  • TAS102
  • bevacizumab
  • avastin
  • RAS status (wild type, mutant)

Last Updated

August 3, 2021