Study of Lenvatinib in Combination With Everolimus in Participants With Unresectable Advanced or Metastatic Renal Cell Carcinoma (RCC)
Condition: Carcinoma, Renal Cell
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: Lenvatinib; Everolimus
Intervention MeSH terms: Everolimus; Lenvatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: lenvatinib; Everolimus; Carcinoma; Unresectable advanced renal cell carcinoma; Metastatic renal cell carcinoma

Summary:

      Phase 1 study to investigate the tolerability and safety of lenvatinib in combination with
      Everolimus in participants with unresectable advanced or metastatic RCC.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Voluntary agreement to provide written informed consent of this study.

          2. Willing and able to comply with all aspects of the protocol after being fully informed
             of the content.

          3. Males or females aged greater than or equal to 20 years at the time of informed
             consent.

          4. Histological or cytological confirmation of RCC.

          5. Participants must have confirmed diagnosis of unresectable advanced and/or metastatic
             RCC.

          6. Disease progression following vascular endothelial growth factor (VEGF) targeted
             therapy.

          7. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 to 1.

          8. Adequately controlled blood pressure with or without the use of antihypertensive
             agents.

          9. Participants with adequate function of major organs.

         10. Adequate blood coagulation function, defined as international normalized ratio (INR)
             less than or equal to 1.5.

         11. Survival expectation of 3 months or longer after study enrollment.

         12. Participants with adequate washout period from the end of prior treatment to the start
             of study drug administration.

         13. Females of childbearing potential must not have had unprotected sexual intercourse
             within 28 days before participant registration and must agree to use a highly
             effective method of contraception throughout the entire study period and for 30 days
             after final administration of investigational drug. If currently abstinent, the
             participant must agree to use a double-barrier method as described above if she
             becomes sexually active during this study period or for 30 days after investigational
             drug discontinuation. Females who are using hormonal contraceptives must have been on
             a stable dose of the same hormonal contraceptive product for at least 4 weeks before
             administration and must continue to use the same contraceptive during this study and
             for 30 days after investigational drug discontinuation.

         14. Male participants and their female partners must meet the criteria above.

        Exclusion Criteria:

          1. Participants with central nervous system (CNS) metastases are not eligible, unless
             they have completed local therapy and have discontinued the use of corticosteroids for
             this indication for at least 4 weeks before starting treatment in this study. Any
             signs (example, radiologic) or symptoms of brain metastases must be stable for at
             least 4 weeks before starting study treatment.

          2. Prior exposure to lenvatinib.

          3. Participants who have not recovered from toxicities to less than or equal to Grade 1
             as a result of prior anticancer therapy, except alopecia.

          4. Major surgery within 3 weeks prior to the first dose of lenvatinib.

          5. Participants with a urine protein greater than or equal to 1 gram per 24 hours (g/24
             hours).

          6. Uncontrollable diabetes as defined by fasting glucose greater than 1.5* upper limit of
             normal (ULN).

          7. Fasting total cholesterol greater than 7.75 millimole per liter (mmol/L) (greater than
             300 milligram per decilitre [mg/dL]).

          8. Fasting triglycerides greater than 2.5 * ULN.

          9. Any condition that might affect the absorption of lenvatinib and/or everolimus.

         10. Significant cardiovascular impairment.

         11. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR
             monitoring.

         12. Active hemoptysis.

         13. Active infections that require systemic treatment.

         14. Human immunodeficiency virus (HIV) positive.

         15. Hepatitis B virus (HBV).

         16. A history of interstitial pneumonia with clinical manifestation or as confirmed by
             means of diagnostic imaging.

         17. Medical need for the continued use of potent or moderate inhibitors of cytochrome P450
             3A (CYP3A) or P-gp, or potent or moderate inducer of CYP3A.

         18. Known intolerance to lenvatinib (or any of the excipients) or known hypersensitivity
             to everolimus (or any of the excipients) or rapmycins (sirolimus, temsirolimus and so
             on).

         19. Alcohol or drug dependency or abuse, inability to comply with every aspects of the
             study protocol, or any physical or mental conditions that in the opinion of the
             investigators would preclude the participant's participation in the study.

         20. Females who are pregnant or breastfeeding (not eligible even she discontinues
             breastfeeding).

         21. Any medical or other condition which, in the opinion of the investigator, would
             preclude participation in a clinical trial.