Clinical Trials /

Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma

NCT02811861

Description:

This is a multicenter, randomized, open-label, Phase 3 study to compare the efficacy and safety of lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) versus sunitinib (Arm C) as first-line treatment in participants with advanced renal cell carcinoma.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
  • Official Title: A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects With Advanced Renal Cell Carcinoma (CLEAR)

Clinical Trial IDs

  • ORG STUDY ID: E7080-G000-307
  • SECONDARY ID: KEYNOTE-581
  • NCT ID: NCT02811861

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
lenvatinibLenvatinib 18 mg plus everolimus 5 mg
everolimusLenvatinib 18 mg plus everolimus 5 mg
pembrolizumabLenvatinib 20 mg plus pembrolizumab 200 mg
SunitinibSunitinib 50 mg

Purpose

This is a multicenter, randomized, open-label, Phase 3 study to compare the efficacy and safety of lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) versus sunitinib (Arm C) as first-line treatment in participants with advanced renal cell carcinoma.

Trial Arms

NameTypeDescriptionInterventions
Lenvatinib 18 mg plus everolimus 5 mgExperimentalLenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily
  • lenvatinib
  • everolimus
Lenvatinib 20 mg plus pembrolizumab 200 mgExperimentalLenvatinib 20 mg administered orally, once daily, plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks
  • lenvatinib
  • pembrolizumab
Sunitinib 50 mgActive ComparatorSunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment
  • Sunitinib

Eligibility Criteria

        Inclusion Criteria:

          -  Histological or cytological confirmation of renal cell carcinoma (RCC) with a
             clear-cell component

          -  At least 1 measurable target lesion according to Response Evaluation in Solid Tumors
             (RECIST) 1.1

          -  Karnofsky Performance Status (KPS) of ≥70

          -  Adequately controlled blood pressure (BP) with or without antihypertensive
             medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive
             medications within 1 week prior to Cycle 1/Day 1 (C1/D1)

          -  Adequate organ function per blood work

        Exclusion Criteria:

          -  Participants who have received any systemic anticancer therapy for RCC, including
             anti-vascular endothelial growth factor (VEGF) therapy, or any systemic
             investigational anticancer agent

          -  Participants with central nervous system (CNS) metastases are not eligible, unless
             they have completed local therapy (eg, whole brain radiation therapy (WBRT), surgery
             or radiosurgery) and have discontinued the use of corticosteroids for this indication
             for at least 4 weeks before starting treatment in this study. Any signs (eg,
             radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before
             starting study treatment

          -  Active malignancy (except for RCC, definitively treated basal or squamous cell
             carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past
             24 months. Participants with history of localized & low risk prostate cancer are
             allowed in the study if they were treated with curative intent and there is no
             prostate specific antigen (PSA) recurrence within the past 5 years

          -  Prior radiation therapy within 21 days prior to start of study treatment with the
             exception of palliative radiotherapy to bone lesions, which is allowed if completed 2
             weeks prior to study treatment start

          -  Received a live vaccine within 30 days of planned start of study treatment

          -  Participants with urine protein ≥1 gram/24 hour

          -  Fasting total cholesterol >300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per
             liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN).
             Note: these participants can be included after initiation or adjustment of
             lipid-lowering medication

          -  Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: these
             participants can be included after initiation or adjustment of glucose-lowering
             medication

          -  Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)

          -  Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The
             degree of tumor invasion/infiltration of major blood vessels should be considered
             because of the potential risk of severe hemorrhage associated with tumor
             shrinkage/necrosis following lenvatinib therapy

          -  Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first
             dose of study drug

          -  Significant cardiovascular impairment within 12 months of the first dose of study
             drug: history of congestive heart failure greater than New York Heart Association
             Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac
             arrhythmia associated with hemodynamic instability. The following is also excluded:
             left ventricular ejection fraction below the institutional normal range as determined
             by multiple-gated acquisition scan or echocardiogram

          -  Active infection (any infection requiring systemic treatment)

          -  Participants known to be positive for Human Immunodeficiency Virus (HIV).

          -  Known active Hepatitis B (eg, Hepatitis B surface antigen (HBsAg) reactive) or
             Hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is
             detected)

          -  Known history of, or any evidence of, interstitial lung disease

          -  Has a history of (non-infectious) pneumonitis that required steroids, or current
             pneumonitis

          -  Participants with a diagnosis of immunodeficiency or who are receiving chronic
             systemic steroid therapy (doses exceeding 10 mg/day of prednisone equivalent) or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of study
             treatment. Physiologic doses of corticosteroids (up to 10 mg/day of prednisone or
             equivalent) may be used during the study

          -  Active autoimmune disease (with the exception of psoriasis) that has required systemic
             treatment in the past 2 years (ie, with use of disease modifying agents,
             corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine,
             insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
             insufficiency) is not considered a form of systemic treatment.

          -  Known intolerance to any of the study drugs (or any of the excipients)

          -  Participant has had an allogenic tissue/solid organ transplant.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) by independent review
Time Frame:up to 43 months approximately
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:Number of participants who discontinued treatment due to toxicity
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:Time to treatment failure due to toxicity
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:Health-Related Quality of Life (HRQoL) scores
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:PFS on next-line of therapy (PFS2)
Time Frame:up to approximately 53 months
Safety Issue:
Description:
Measure:PFS by investigator assessment
Time Frame:up to 53 Months approximately
Safety Issue:
Description:
Measure:Model-predicted clearance for lenvatinib and everolimus
Time Frame:0.5-4 hours (h) and 6-10 h postdose on Cycle 1 Day 1; predose and 2-12 h postdose on Cycle 1 Day 15; predose and 0.5-4 h and 6-10 h postdose on Cycle 2 Day 1; predose on Day 1 of Cycles 3, 4, 5, and 6
Safety Issue:
Description:
Measure:AUC for lenvatinib and everolimus
Time Frame:0.5-4 h and 6-10 h postdose on Cycle 1 Day 1; predose and 2-12 h postdose on Cycle 1 Day 15; predose and 0.5-4 h and 6-10 h postdose on Cycle 2 Day 1; predose on Day 1 of Cycles 3, 4, 5, and 6
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • Renal Cell Carcinoma (RCC)
  • Lenvatinib
  • First-line RCC
  • Treatment-naive RCC
  • Everolimus
  • Pembrolizumab
  • Sunitinib
  • Phase 3 RCC
  • Phase 3 first-line RCC
  • Phase 3 treatment-naive RCC

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