Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients
Condition: Refractory Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Trifluridine/Tipiracil; Bevacizumab
Intervention description: Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; administered every 2 weeks (Day 1 and Day 15)
Intervention MeSH terms: Trifluridine; Bevacizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 492.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: trifluridine/tipiracil/lonsurf; TAS102; bevacizumab; avastin; RAS status (wild type, mutant)

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.
    

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.