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

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ClinicalTrials.gov Identifier: NCT02811861
Recruitment Status : Recruiting
First Posted : June 23, 2016
Last Update Posted : December 14, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: lenvatinib Drug: everolimus Drug: pembrolizumab Drug: Sunitinib Phase 3

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : October 13, 2016
Estimated Primary Completion Date : October 15, 2019
Estimated Study Completion Date : January 15, 2020

Arms and Interventions

Arm Intervention/treatment
Experimental: Lenvatinib 18 mg plus everolimus 5 mg
Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily
Drug: lenvatinib Drug: everolimus
Experimental: Lenvatinib 20 mg plus pembrolizumab 200 mg
Lenvatinib 20 mg administered orally, once daily, plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks
Drug: lenvatinib Drug: pembrolizumab
Active Comparator: Sunitinib 50 mg
Sunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment
Drug: Sunitinib

Outcome Measures

Primary Outcome Measures :
  1. Progression-free survival (PFS) by independent review [ Time Frame: up to 37 months approximately ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: up to approximately 37 months ]
  2. Overall survival (OS) [ Time Frame: up to approximately 37 months ]
  3. Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: up to approximately 37 months ]
  4. Number of participants who discontinued treatment due to toxicity [ Time Frame: up to approximately 37 months ]
  5. Time to treatment failure due to toxicity [ Time Frame: up to approximately 37 months ]
  6. Health-Related Quality of Life (HRQoL) scores [ Time Frame: up to approximately 37 months ]
  7. PFS on next-line of therapy (PFS2) [ Time Frame: up to approximately 37 months ]
  8. PFS by investigator assessment [ Time Frame: Upto 37 Months approximately ]
  9. Model-predicted clearance for lenvatinib, everolimus and pembrolizumab [ Time Frame: lenvatinib & everolimus: 0.5-4h,6-10h postdose on C1D1; predose 2-12h postdose C1D15;predose 0.5-4,6-10 h postdose on C2D1; predose on D1 of C 3,4,5,6. Pembrolizumab: predose on Day 1 of C 1,2,3,5, and off-treatment visit; end of infusion on C1D1, C2D1 ]
  10. AUC for lenvatinib, everolimus and pembrolizumab [ Time Frame: lenvatinib & everolimus:0.5-4h, 6 -10h postdose C1D1; predose, 2-12h postdose on C1D15; predose 0.5-4,6-10 h,postdose C2D1, predose D1 of C 3, 4, 5, 6. Pembrolizumab: predose Day 1 of Cycles 1, 2, 3, 5, off-treatment visit; end of infusion on C1D1, C2D1 ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  • Subjects 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 brain 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. Subjects 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 subjects 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 subjects 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 subjects 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 6 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke, cardiac arrhythmia associated with significant cardiovascular impairment, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multiple gated acquisition scan (MUGA) 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 systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5 mg/day of prednisone or equivalent) may be approved after consultation with the sponsor
  • 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)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02811861

Contact: Eisai Medical Information 1-888-274-2378 esi_medinfo@eisai.com

  Show 117 Study Locations
Sponsors and Collaborators
Eisai Inc.
More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT02811861     History of Changes
Other Study ID Numbers: E7080-G000-307
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: December 14, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Eisai Inc.:
Renal Cell Carcinoma (RCC)
First-line RCC
Treatment-naive RCC
Phase 3 RCC
Phase 3 first-line RCC
Phase 3 treatment-naive RCC

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors