Advanced Renal Cell Carcinoma Kindney Cancer
Conditions
Interventions
Test Arm (Arm A): Lenvatinib is provided as 4-mg and 10-mg capsules. Everolimus
is provided as 5-mg tablets. Lenvatinib 18 mg (one 10-mg plus two 4-mg
capsules) plus everolimus 5 mg will be taken or
Sponsors
Eisai
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable). 2. Documented evidence of advanced RCC. 3. 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. 4. 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 5. Karnofsky Performance Status (KPS) of >=70. 6. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP 1.5×ULN, the calculated creatinine clearance >=30 mL/min (per the Cockcroft-Gault formula) is acceptable. 8. Adequate bone marrow function defined by: • Absolute neutrophil count (ANC) >=1500/mm3 • Platelets >=100,000/mm3 • Hemoglobin >=9 g/dL. 9. Adequate blood coagulation function defined by International Normalized ratio (INR) 3xULN and known to have bone metastases can be included. 11. Provide written informed consent. 12. Willing and able to comply with all aspects of the protocol.
Exclusion criteria
Exclusion criteria: 1. Subjects who have received any systemic anticancer therapy for RCC, including anti-VEGF therapy, or any systemic investigational anticancer agent. Prior adjuvant treatment with an investigational anticancer agent is not allowed unless the investigator can provide evidence of subject's randomization to placebo arm. 2. Subjects with 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 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. Subjects who are using other investigational agents or who had received investigational drugs 1+ on urine dipstick testing 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, everolimus, and/or sunitinib. 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 wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Progression-free survival (PFS) by independent review is defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurs first) as determined by IIR using RECIST 1.1. PFS censoring rules will follow the FDA guidance of 2007; specifics of this will be detailed in the Statistical Analysis Plan. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Objective response rate (ORR) is defined as the proportion of subjects who have best overall response of CR or PR as determined by IIR using RECIST 1.1. • Overall survival (OS) is defined as the time from the date of randomization to the date of death from any cause. Subjects who are lost to follow-up and those who are alive at the date of data cut-off will be censored at the date the subject was last known alive, or date of data cut-off, whichever occurs first. • Safety will be assessed summarizing the incidence of treatmentemergent adverse events (TEAEs) and SAEs together with all other safety parameters. • Proportion of subjects who discontinued treatment due to toxicity is defined as the proportion of subjects who discontinue study treatment due to treatment-emergent adverse events (TEAEs). • Time to treatment failure due to toxicity is defined as the time from the date of first dose to the date that a subject discontinues study treatment due to TEAEs. • Health-Related Quality of Life (HRQoL) will be assessed using the Functional Assessment of Cancer Therapy Kidney Syndrome Index- Disease-Related Symptom (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. • PFS on next-line of therapy (PFS2) is defined as the time from randomization to disease progression on next-line of treatment, or death from any cause, (whichever occurs first). | — |
Countries
Netherlands
Outcome results
None listed