Renal Cell Carcinoma
Conditions
Interventions
The patient will be assigned to one of the two treatment groups and will
receive a starting dose of either:
• Group A lenvatinib 18mg and everolimus 5mg orally once daily or
• Group B lenvatinib 14m
Sponsors
Eisai
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmation of predominant clear cell RCC (original tissue diagnosis of RCC is acceptable)., 2. Documented evidence of advanced RCC., 3. One prior disease progression episode on or after VEGF-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, cabozantinib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) administered for the treatment of RCC. Prior PD-1/PD-L1 treatment in addition to 1 prior VEGF-targeted treatment is allowed., 4. At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:, Lymph node (LN) lesion that measures at least 1 dimension as >=1.5 cm in the short axis Non-nodal lesion that measures >=1.0 cm in the longest diameter, The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion., 5. Male or female subjects age >=18 years (or any age >18 years if that age is considered to be an adult per the local jurisdiction) at the time of informed consent., 6. Karnofsky Performance Status (KPS) of >=70., 7. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =30 mL/min per the Cockcroft and Gault formula (Appendix 1)., 9. Adequate bone marrow function defined by:, Absolute neutrophil count (ANC) >=1500/mm3 (>=1.5 x 109/L) Platelets >=100,000/ mm3(>=100 x 109/L) Hemoglobin >=9 g/dL., 10. Adequate blood coagulation function defined by International Normalized Ratio (INR)
Exclusion criteria
Exclusion criteria: 1. More than 1 prior VEGF-targeted treatment for advanced RCC., 2. Subjects with Central Nervous System (CNS) metastases are not eligible, unless they have completed local therapy for at least 4 weeks and have discontinued the use of corticosteroids for this indication or are on a tapering regimen of corticosteroids (defined as 1 + on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Subjects with urine protein >=1 g/24 h will be ineligible., 8. Fasting total cholesterol > 300 mg/dL (or > 7.75 mmol/L) and/or fasting triglycerides level > 2.5 x ULN. NOTE: these subjects can be included after initiation or adjustment of lipid-lowering medication., 9. 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., 10. Prolongation of QTc interval to > 480 ms., 11. Subjects who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy., 12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib or everolimus., 13. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (eg, carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy., 14. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug., 15. Significant cardiovascular impairment within 6 months prior to 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 left ventricular ejection fraction (LVEF) below the institutional normal range as determined by screening multigated acquisition (MUGA) scan or echocardiogram., 16. Active infection (any infection requiring systemic treatment)., 17.Any medical or other condition that in the opinion of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoints • Objective response rate (ORR) at Week 24 (ORR24W) as assessed by the investigator according to RECIST 1.1. ORR24W is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR) at the Week¬24 (after randomization) time point or earlier. To be considered a BOR, all responses must be confirmed no less than 4 weeks after the initial assessment of response. • Proportion of subjects with intolerable Grade 2 and any >= Grade 3 TEAEs within 24 weeks after randomization (as of the Week-24 time point). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints • Progression-free survival (PFS), defined as the time from the date of randomization to the date of first documentation of disease progression or date of death, whichever occurs first. PFS censoring rules will be defined in the statistical analysis plan (SAP) and will follow FDA guidance. • ORR as assessed by the investigator according to RECIST 1.1 at the end of treatment. ORR is defined as the proportion of subjects with BOR of CR or PR at the end of treatment. To be considered BOR, all responses must be confirmed no less than 4 weeks after the initial assessment of response. • Overall safety profile and tolerability of lenvatinib in combination with everolimus. • Proportion of subjects who discontinue treatment due to toxicity, defined as the proportion of subjects who discontinue study treatment due to TEAEs. • Time to treatment failure due to toxicity, defined as the time from the date of randomization to the date that a subject discontinues study treatment due to TEAEs. • Lenvatinib and everolimus exposure parameters and PK and PD drug-drug interactions. • Overall survival (OS), measured from the date of randomization until date of death from any cause. In the absence of confirmation of death, subjects will be censored either at the date that the subject was last known to be alive or the date of data cutoff, whichever comes earlier. • Health-Related Quality of Life (HRQoL) will be assessed using the Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS), the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 and the European Quality of Life (EuroQol) EQ-5D-3L instruments. • PFS2, defined as the time from randomization to the date of disease progression after next line of therapy or death from any cause, whichever occurs first. PFS2 censoring rules will be defined in the SAP. | — |
Countries
Netherlands
Outcome results
None listed