envatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
- Conditions
- Renal Cell Carcinoma
- Registration Number
- JPRN-jRCT2080223751
- Lead Sponsor
- Eisai Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 1050
(1)Histological or cytological confirmation of renal cell carcinoma (RCC) with a clear-cell component
(2)At least 1 measurable target lesion according to Response Evaluation in Solid Tumors (RECIST) 1.1
(3)Karnofsky Performance Status (KPS) of >=70
(4)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)
(5)Adequate organ function per blood work
(6)Male or female subjects age >=18 years (or any age greater than 18 years of age if that age is considered to be an adult per the local jurisdiction) at the time of informed consent
(1)Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent
(2)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
(3)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
(4)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
(5)Received a live vaccine within 30 days of planned start of study treatment
(6)Participants with urine protein >=1 gram/24 hour
(7)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
(8)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
(9)Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)
(10)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
(11)Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
(12)Significant cardiovascular impairment within 12 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 cerebrovascular accident (CVA) or cardiac arrhythmia associated with hemodynamic instabilityt, or a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multiple gated acquisition scan (MUGA) or echocardiogram
(13)Active infection (any infection requiring systemic treatment)
(14)Participants known to be positive for Human Immunodeficiency Virus (HIV).
(15)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)
(16)Known history of, or any evidence of, interstitial lung disease
(17)Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
(18)Participants with a diagnosis of immunodeficiency or who are receiving chronic systemic steroid therapy (at doses exceeding 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method efficacy<br>Progression-free survival (PFS) by independent review
- Secondary Outcome Measures
Name Time Method safety<br>efficacy<br>pharmacokinetics<br>-Objective response rate (ORR)<br>-Overall survival (OS) <br>-Number of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)<br>-Number of participants who discontinued treatment due to toxicity <br>-Time to treatment failure due to toxicity<br>-Health-Related Quality of Life (HRQoL) scores <br>-PFS on next-line of therapy (PFS2)<br>-PFS by investigator assessment <br>-Model-predicted clearance for lenvatinib and everolimus<br>-AUC for lenvatinib and everolimus