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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002778-11 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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Study E7080-G000-218 is a Randomized, open-label (formerly Double-blind), Phase 2 Trial conducted to assess whether a starting dose of lenvatinib 14 milligrams (mg) in combination with everolimus 5 mg once daily (QD) will provide comparable efficacy (based on objective response rate [ORR] at 24 weeks [ORR24W]) with an improved safety profile compared to lenvatinib 18 mg in combination with everolimus 5 mg (based on treatment-emergent intolerable Grade 2, or any greater than or equal to (>=) Grade 3 adverse events (AEs) in the first 24 weeks after randomization).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lenvatinib 14 mg plus everolimus 5 mg | Experimental | Participants will receive oral lenvatinib 14 mg once daily (QD) plus oral everolimus 5 mg QD as the starting dose for Cycle 1. If there are no intolerable Grade 2 or any >= Grade 3 treatment-emergent adverse events (TEAEs) that require dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), the lenvatinib dose will be escalated to 18 mg QD (plus everolimus 5 mg) beginning in Cycle 2 or later (cycle length equal to [=] 28 days) during randomization phase. After the data cutoff for the primary analysis, participants will receive study treatment as continuous 56-day cycles. |
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| Lenvatinib 18 mg plus everolimus 5 mg | Experimental | Participants will receive oral lenvatinib 18 mg QD plus oral everolimus 5 mg QD as the starting dose in Cycle 1 or later (cycle length =28 days) during randomization phase. After the data cutoff for the primary analysis, participants will receive study treatment as continuous 56-day cycles. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lenvatinib | Drug | lenvatinib capsules. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate at Week 24 (ORR24W) | ORR24W was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at the Week 24 (after randomization) time point, during treatment or within 28 days after the last dose date but on or prior to the start of new anticancer therapy based on investigator assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeters (mm). PR: defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. | At Week 24 |
| Percentage of Participants With Intolerable Grade 2 or Any Grade >=Grade 3 TEAEs Within 24 Weeks | TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. | Up to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS was defined as the time from the date of randomization to the date of the first documentation of PD by investigator assessment or date of death, whichever occurred first according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter (SOD) of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% confidence interval (CI). As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. |
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Inclusion Criteria:
Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable)
Documented evidence of advanced RCC
One prior disease progression episode on or after vascular endothelial growth factor (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 programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) treatment in addition to 1 prior VEGF-targeted treatment is allowed.
At least 1 measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) meeting the following criteria:
Male or female participants 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
Karnofsky Performance Status (KPS) of >=70
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to (<=) 150/90 millimeters of mercury (mmHg) at Screening and no change in antihypertensive medications within 1 week before Cycle 1/Day 1
Adequate renal function defined as calculated creatinine clearance >=30 milliliters per minute (mL/min) per the Cockcroft and Gault formula
Adequate bone marrow function defined by:
Adequate blood coagulation function defined by International Normalized Ratio (INR) <=1.5 (except for participants on warfarin therapy where INR must be <=3.0 prior to randomization)
Adequate liver function defined by:
Participant must voluntarily agree to provide written informed consent
Participant must be willing and able to comply with all aspects of the protocol
Exclusion Criteria:
More than 1 prior VEGF-targeted treatment for advanced RCC
Participants 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 <=10 mg prednisolone equivalent) before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
Active malignancy (except for RCC or definitively treated basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months
Any anti-cancer treatment (except for radiation therapy) within 21 days, or any investigational agent within 30 days prior to the first dose of study drug; participants should have recovered from any toxicity related to previous anti-cancer treatment to Common Toxicity Criteria (CTC) grade 0 or 1.
Prior radiation therapy within 21 days prior to the 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
Known intolerance to study drug (or any of the excipients) and/or known hypersensitivity to rapamycins (example, sirolimus, everolimus, temsirolimus) or any of the excipients
Participants with proteinuria greater than (>) 1+ on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 g/24 hour will be ineligible.
Fasting total cholesterol ˃300 mg/dL (or ˃7.75 millimoles [mmol]/L) and/or fasting triglycerides level ˃2.5* the 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 QT corrected (QTc) interval to >480 milliseconds (ms)
Participants who have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy
Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib or everolimus
Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (example, carotid artery) 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 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, or 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.
Active infection (any infection requiring systemic treatment)
Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [β-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of β-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
Females of childbearing potential who (Note: all females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing].):
do not agree to use a highly effective method of contraception for the entire study period and for up to 8 weeks after study drug discontinuation, that is:
do not have a vasectomized partner with confirmed azoospermia
For sites outside of the European Union, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception, that is, double barrier methods of contraception, such as condom plus diaphragm or cervical/vault cap with spermicide.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope National Medical Center | Duarte | California | 91010 | United States | ||
| Innovative Clinical Research Institute, LLC |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35881028 | Derived | Bergerot C, Young Rha S, Pal S, Koralewski P, Stroyakovskiy D, Alekseev B, Parnis F, Castellano D, Lyun Lee J, Sunela K, Ciuleanu T, Heng D, Glen H, Wang J, Bennett L, Pan J, O'Hara K, Puente J. Health-Related Quality of Life Outcomes With Two Different Starting Doses of Lenvatinib in Combination With Everolimus for Previously Treated Renal Cell Carcinoma. Oncologist. 2023 Jan 18;28(1):59-71. doi: 10.1093/oncolo/oyac142. |
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A total of 489 participants were screened, of which 146 were screen failures and 343 were enrolled and randomized, out of which 341 participants were treated.
Participants took part in the study at 82 investigative sites in Australia, Korea, Taiwan, Czech, Poland, Romania, Russia, Finland, Greece, Italy, Netherlands, Portugal, Spain, United Kingdom, Canada and the United States from 17 August 2017 to 20 June 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lenvatinib 14 mg + Everolimus 5 mg | Participants received lenvatinib 14 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until progressive disease (PD), development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. Participants who had no intolerable Grade 2 or any greater than or equal to (>=) Grade 3 treatment-emergent adverse events (TEAEs) that required dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), had lenvatinib dose titrated to 18 mg once daily (along with everolimus 5 mg) beginning in Cycle 2 or later (cycle length equals to (=) 28 days) during randomization phase. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 11, 2020 | Jan 28, 2021 |
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Study was initially double-blind.
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| everolimus | Drug | everolimus tablets. |
|
| From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to date of data cutoff for the primary analysis (up to 29 months) |
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants with a BOR of CR or PR at the at the end of treatment based on investigator assessment according to RECIST v1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR: defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | From date of randomization up to first documentation of PD or date of death, whichever occurred first or up to the date of data cut off for the primary analysis (up to 29 months) |
| Number of Participants With TEAEs and Serious TEAEs | TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. | From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months) |
| Percentage of Participants Who Discontinued Treatment Due to Toxicity | Percentage of participants who discontinued treatment due to toxicity, defined as the percentage of participants who discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to NCI-CTCAE v4.03. | From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months) |
| Time to Treatment Failure Due to Toxicity | Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date that a participant discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to CTCAE v4.03. As planned, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | From the date of randomization to the date of discontinuation of study treatment due to TEAEs, or date of data cut off for the primary analysis (up to 29 months) |
| Plasma Concentration of Lenvatinib | PK sparse sampling was performed. As planned, the post-dose plasma sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Whole Blood Concentration of Everolimus | PK sparse sampling was performed. As planned, the post-dose whole blood sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib Alone and When Coadministration With Everolimus in Renal Cell Carcinoma (RCC) Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib CL/F value was derived from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Model Predicted Dose Normalized Area Under the Plasma Concentration-time Curve (AUC) for Lenvatinib Alone and When Coadministration With Everolimus in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Model Predicted CL/F for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus CL/F value was derived from the final PK model. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Model Predicted Dose Normalized AUC for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
| Overall Survival (OS) | OS was defined as the time from the date of randomization until the date of death from any cause. In the absence of confirmation of death, participants will be censored either at the date that the participant was last known to be alive or the date of data cutoff for the primary analysis, whichever comes earlier. Median OS was to be calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | From the date of randomization until the date of death from any cause, or up to date of data cut off for the primary analysis (up to 29 months) |
| Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores | The FKSI-DRS consisted of 9 items that experts and participants had indicated are important targets for the treatment of advanced kidney cancer, and that clinical experts had indicated are primarily disease-related, as opposed to treatment-related. Symptoms assessed on the FKSI-DRS included lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or hematuria. Each item was scored on a 5-point Likert-type scale (0 = not at all; 4 = very much) where total score ranged from 0 (worst) to 36 (best), where higher scores correspond to better outcomes. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
| HRQoL Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Scores | The EORT QLQ-C30 consisted of 30 questions comprising 9 multiple-item scales and 6 single items. Multiple-item scales of QLQ-C30 consisted of 5 functional scales (physical, role, emotional, cognitive, and social) and 3 symptom scales (fatigue, nausea and vomiting, pain) and a global health status/QOL score. Six single-item scales of QLQ-C30 involved dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. First 28 questions used a 4-point scale (1 = Not at all to 4 = Very much); and last 2 questions used a 7-point scale (1 = Very poor to 7 = Excellent). Scores for all scales range from 0 to 100. For the overall HRQoL and functioning scales, a higher score was correlated with better HRQoL, whereas a higher score for symptom scales represented worse HRQoL. As pre-specified in protocol, data for secondary outcome measure was collected and analyzed till primary analysis only. | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
| HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS) | The EQ-5D-3L is a health profile questionnaire assessing quality of life along 5 dimensions. Participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. The EQ-5D index was calculated by applying preference-based weights (tariffs) to the scores of the five health state dimensions. Index values can range from -1 to 1, with 0 representing a health state equivalent to death and 1 representing perfect health. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
| Progression-free Survival After Next Line of Therapy (PFS2) | PFS2, defined as the time from randomization to the date of PD after next line of therapy or death from any cause, whichever occurred first based on investigator assessment according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS2 was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% CI. As pre-specified in protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | From the time of randomization to the date of PD after next line of therapy or death from any cause or the date of data cutoff for the primary analysis, whichever occurs first (up to 29 months) |
| Whittier |
| California |
| 90603 |
| United States |
| Baptist Health Medical Group Oncology, LLC - US Oncology | Miami | Florida | 33143 | United States |
| Optimal Research | Honolulu | Hawaii | 96819 | United States |
| Oklahoma Cancer Specialist and Research Institute , LLC | Tulsa | Oklahoma | 74146 | United States |
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15232 | United States |
| University of Tennessee Medical Center | Knoxville | Tennessee | 37920 | United States |
| Texas Oncology PA - US Oncology | Fort Worth | Texas | 76104 | United States |
| Macquarie University | Macquarie Park | New South Wales | Australia |
| Northern Cancer Institute, Saint Leonards | Saint Leonards | New South Wales | Australia |
| Adelaide Cancer Center | Kurralta Park | South Australia | Australia |
| Sunshine Hospital | Saint Albans | Victoria | Australia |
| Fiona Stanley Hospital | Murdoch | Western Australia | Australia |
| Alberta Health Service - Tom Baker Cancer Centre | Calgary | Alberta | T2N 4N2 | Canada |
| British Columbia Cancer Agency | Kelowna | British Columbia | V1Y 5L3 | Canada |
| Juravinski Cancer Centre | Hamilton | Ontario | L8V 5C2 | Canada |
| London Health Sciences Centre | London | Ontario | N6A 4L6 | Canada |
| Ottawa Hospital Cancer Centre | Ottawa | Ontario | K1H 8L6 | Canada |
| Sunnybrook Research Institute- University of Toronto | Toronto | Ontario | M4N 3M5 | Canada |
| Sir Mortimer B Davis Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Masarykuv onkologicky ustav | Brno | Czechia |
| Fakultni nemocnice Olomouc | Olomouc | Czechia |
| Fakultni nemocnice v Motole | Prague | Czechia |
| Nemocnice Na Bulovce | Prague | Czechia |
| Helsingin Yliopistollinen Keskussairaala | Helsinki | Finland |
| Tampereen yliopistollinen sairaala | Tampere | Finland |
| Turun Yliopistollinen Keskussairaala | Turku | Finland |
| Vaasan Keskussairaala | Vaasa | Finland |
| Alexandra Hospital | Athens | Greece |
| Metropolitan hospital | Athens | Greece |
| University General Hospital of Patras | Pátrai | Greece |
| Interbalkan Medical Center of Thessaloniki | Pylaia | Greece |
| EUROMEDICA General Clinic of Thessaloniki | Thessaloniki | Greece |
| Papageorgiou General Hospital of Thessaloniki | Thessaloniki | Greece |
| IRCCS Istituto Nazionale dei Tumori | Milan | Lombardy | Italy |
| Presidio Ospedaliero San Donato | Arezzo | 52100 | Italy |
| AORN A Cardarelli | Naples | Italy |
| Azienda Ospedaliera San Camillo Forlanini | Roma | 00152 | Italy |
| Leids Universitair Medisch Centrum | Leiden | Netherlands |
| Hagaziekenhuis | The Hague | Netherlands |
| MC Haaglanden | The Hague | Netherlands |
| Szpital Specjalistyczny w Brzozowie | Brzozów | Poland |
| Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii | Gdansk | Poland |
| NZOZ Vesalius | Krakow | Poland |
| SP ZOZ Szpital Uniwersytecki w Krakowie | Krakow | Poland |
| Centrum Onkologii Ziemi Lubelskiej | Lublin | Poland |
| Samodzielny Publiczny Zaklad Opieki Zdrowotnej Opolskie Centrum Onkologii | Opole | Poland |
| Mrukmed. Lekarz Beata Madej-Mruk i Partner. Spolka Partnerska | Rzeszów | Poland |
| MAGODENT Sp. z o.o. Szpital Elblaska | Warsaw | Poland |
| Centro Hospitalar E Universitário de Coimbra EPE | Coimbra | Portugal |
| Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria | Lisbon | Portugal |
| Champalimaud Cancer Center | Lisbon | Portugal |
| Centro Hospitalar do Porto - Hospital de Santo António | Porto | Portugal |
| Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe | Porto | Portugal |
| Medisprof SRL | Cluj-Napoca | Romania |
| Prof Dr I Chiricuta Institute of Oncology | Cluj-Napoca | Romania |
| Oncology Center Sfantul Nectarie | Craiova | Romania |
| Oncocenter Clinical Oncology | Timișoara | Romania |
| Altay Regional Oncology Center | Barnaul | Russia |
| Chelyabinsk Regional Clinical Oncology Dispensary | Chelyabinsk | Russia |
| Central Clinical Hospital With Polyclinic of President Administration of RF | Moscow | Russia |
| Moscow City Oncology Hospital #62 | Moscow | Russia |
| Moscow Scientific Research Oncology Institute P.A. Herzen | Moscow | Russia |
| Federal State Institution Medical Radiology Research Center | Obninsk | Russia |
| Clinical Oncology Dispensary | Omsk | Russia |
| Regional Clinical Oncology Hospital | Yaroslavl | Russia |
| National Cancer Center | Goyang-si | Gyeonggido | South Korea |
| Chonnam National University Hwasun Hospital | Jeonam | South Korea |
| Asan Medical Center | Seoul | South Korea |
| Samsung Medical Center | Seoul | South Korea |
| Severance Hospital - Yonsei University Health System | Seoul | South Korea |
| The Catholic University of Korea, Seoul Saint Mary's Hospital | Seoul | South Korea |
| Hospital Universitario A Coruna | A Coruña | Spain |
| Hospital Universitario Germans Trias i Pujol | Badalona | Spain |
| Hospital Clinic de Barcelona | Barcelona | Spain |
| Hospital de la Santa Creu I Sant Pau | Barcelona | Spain |
| C.H. Regional Reina Sofia | Córdoba | Spain |
| ICO l'Hospitalet - Hospital Duran i Reynals | L'Hospitalet de Llobregat | Spain |
| Hospital Clinico San Carlos | Madrid | 28040 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | Spain |
| Hospital Universitario Ramon y Cajal | Madrid | Spain |
| MD Anderson Cancer Center Madrid | Madrid | Spain |
| Hospital Universitario Son Espases | Palma de Mallorca | Spain |
| Clinica Universidad Navarra | Pamplona | Spain |
| Fundacion Instituto Valenciano de Oncologia | Valencia | Spain |
| China Medical University Hospital | Taichung | Taiwan |
| Taichung Veterans General Hospital | Taichung | Taiwan |
| National Taiwan University Hospital | Taipei | Taiwan |
| Taipei Veterans General Hospital | Taipei | Taiwan |
| Beatson West of Scotland Cancer Centre | Glasgow | United Kingdom |
| Christie Hospital | Manchester | United Kingdom |
| Mount Vernon Hospital | Northwood | United Kingdom |
| Singleton Hospital | Swansea | United Kingdom |
| FG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
| Treated Participants |
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| Safety Set | One participant was randomized to lenvatinib 18 mg arm but received lenvatinib 14 mg as the starting dose and therefore was included in lenvatinib 14 mg arm in safety population. |
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| COMPLETED |
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| NOT COMPLETED |
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Full analysis set (FAS) included all randomized participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lenvatinib 14 mg + Everolimus 5 mg | Participants received lenvatinib 14 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. Participants who had no intolerable Grade 2 or any >=Grade 3 TEAEs that required dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), had lenvatinib dose titrated to 18 mg once daily (along with everolimus 5 mg) beginning in Cycle 2 or later (cycle length =28 days) during randomization phase. |
| BG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Objective Response Rate at Week 24 (ORR24W) | ORR24W was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) at the Week 24 (after randomization) time point, during treatment or within 28 days after the last dose date but on or prior to the start of new anticancer therapy based on investigator assessment according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 10 millimeters (mm). PR: defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. | Per-protocol analysis set 1 (PPAS1) included all randomized participants minus the 32 participants who had received >=2 incorrect lenvatinib doses due to interactive voice and web response system (IxRS) issues. | Posted | Number | 95% Confidence Interval | percentage of participants | At Week 24 |
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| Primary | Percentage of Participants With Intolerable Grade 2 or Any Grade >=Grade 3 TEAEs Within 24 Weeks | TEAE was defined as an adverse event (AE) with an onset that had occurred after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. | Per-protocol safety analysis set included all randomized and treated participants minus 32 participants who had received >=2 incorrect lenvatinib doses due to IxRS issues according to actual treatment received. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to Week 24 |
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| Secondary | Progression-free Survival (PFS) | PFS was defined as the time from the date of randomization to the date of the first documentation of PD by investigator assessment or date of death, whichever occurred first according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter (SOD) of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% confidence interval (CI). As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | PPAS1 included all randomized participants minus the 32 participants who had received >=2 incorrect lenvatinib doses due to IxRS issues. | Posted | Median | 95% Confidence Interval | months | From the date of randomization to the date of the first documentation of PD or date of death, whichever occurred first or up to date of data cutoff for the primary analysis (up to 29 months) |
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| Secondary | Objective Response Rate (ORR) | ORR was defined as the percentage of participants with a BOR of CR or PR at the at the end of treatment based on investigator assessment according to RECIST v1.1. CR: defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to <10 mm. PR: defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be considered a BOR, all responses had to be confirmed no less than 4 weeks after the initial assessment of response. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | PPAS1 included all randomized participants minus the 32 participants who had received >=2 incorrect lenvatinib doses due to IxRS issues. | Posted | Number | 95% Confidence Interval | percentage of participants | From date of randomization up to first documentation of PD or date of death, whichever occurred first or up to the date of data cut off for the primary analysis (up to 29 months) |
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| Secondary | Number of Participants With TEAEs and Serious TEAEs | TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A serious adverse event (SAE) was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. | Safety analysis set (SAS) included all participants who were randomized and received at least 1 dose of study drug according to the treatment starting dose actually received. | Posted | Count of Participants | Participants | From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months) |
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| Secondary | Percentage of Participants Who Discontinued Treatment Due to Toxicity | Percentage of participants who discontinued treatment due to toxicity, defined as the percentage of participants who discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to NCI-CTCAE v4.03. | FAS included all randomized participants. | Posted | Number | percentage of participants | From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months) |
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| Secondary | Time to Treatment Failure Due to Toxicity | Time to treatment failure due to toxicity was defined as the time from the date of randomization to the date that a participant discontinued study treatment due to TEAEs. Toxicity (except hypertension and non-infectious pneumonitis) was assessed according to CTCAE v4.03. As planned, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | FAS included all randomized participants. | Posted | Median | Full Range | months | From the date of randomization to the date of discontinuation of study treatment due to TEAEs, or date of data cut off for the primary analysis (up to 29 months) |
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| Secondary | Plasma Concentration of Lenvatinib | PK sparse sampling was performed. As planned, the post-dose plasma sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints. | Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable lenvatinib plasma or everolimus whole blood concentration data. Here, "overall number of participants analyzed" are the participants who were evaluable for the outcome measure and "number analyzed" were the participants who were evaluable for this outcome measure at given time points. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Whole Blood Concentration of Everolimus | PK sparse sampling was performed. As planned, the post-dose whole blood sample was collected anytime between 0.5 to 4 hours at Cycle 1 Days 1 and 15, between 6 to 10 hours at Cycle 1 Days 1 and 15, and between 2 to 12 hours at Cycle 2 Day 1. Only one sample was collected for each post-dose category between specified timepoints. | PK analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable lenvatinib plasma or everolimus whole blood concentration data. Here, "overall number of participants analyzed" are the participants who were evaluable for the outcome measure and "number analyzed" were the participants who were evaluable at given time points. | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib Alone and When Coadministration With Everolimus in Renal Cell Carcinoma (RCC) Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib CL/F value was derived from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only. | PK analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable lenvatinib plasma concentration data. Population included participants from E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and current study E7080-G000-218 (NCT03173560). Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Model Predicted Dose Normalized Area Under the Plasma Concentration-time Curve (AUC) for Lenvatinib Alone and When Coadministration With Everolimus in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The lenvatinib concentration data was pooled from studies E7080 -G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for lenvatinib was fitted to the pooled dataset. Individual lenvatinib AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model. The outcome measure was assessed for lenvatinib 18 mg dose only. | PK analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable lenvatinib plasma concentration data. Population included participants from E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and current study E7080-G000-218 (NCT03173560). Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | nanogram*hour per milliliter (ng*h/mL) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Model Predicted CL/F for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus CL/F value was derived from the final PK model. | PK analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable everolimus whole blood concentration data. Population included participants from E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or current study E7080-G000-218 (NCT03173560). Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Model Predicted Dose Normalized AUC for Everolimus Alone and When Coadministration With Lenvatinib in RCC Participants to Assess Drug-Drug Interaction | Sparse PK samples were collected and analyzed using a population PK approach to estimate PK parameters. The everolimus concentration data was pooled from studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or from current study E7080-G000-218 (NCT03173560). A previously developed 3-compartment PK model for everolimus was fitted to the pooled dataset. Individual everolimus AUC at steady state based on the starting dose was derived as a function of starting dose from the final PK model. | PK analysis set included all participants who received at least 1 dose of study drug with documented dosing history and had at least 1 evaluable everolimus whole blood concentration data. Population included participants from E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or current study E7080-G000-218 (NCT03173560). Here, "overall number of participants analyzed" are the participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | ng*hour/mL | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose, 0.5-4 hours and 6-10 hours post-dose; Cycle 2 Day 1: pre-dose and 2-12 hours post-dose (each cycle length =28 days) |
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| Secondary | Overall Survival (OS) | OS was defined as the time from the date of randomization until the date of death from any cause. In the absence of confirmation of death, participants will be censored either at the date that the participant was last known to be alive or the date of data cutoff for the primary analysis, whichever comes earlier. Median OS was to be calculated using Kaplan-Meier estimate and presented with 2-sided 95% confidence interval. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | PPAS1 included all randomized participants minus the 32 participants who had received >=2 incorrect lenvatinib doses due to IxRS issues. | Posted | Median | 95% Confidence Interval | months | From the date of randomization until the date of death from any cause, or up to date of data cut off for the primary analysis (up to 29 months) |
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| Secondary | Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores | The FKSI-DRS consisted of 9 items that experts and participants had indicated are important targets for the treatment of advanced kidney cancer, and that clinical experts had indicated are primarily disease-related, as opposed to treatment-related. Symptoms assessed on the FKSI-DRS included lack of energy, fatigue, weight loss, pain, bone pain, shortness of breath, cough, fever, or hematuria. Each item was scored on a 5-point Likert-type scale (0 = not at all; 4 = very much) where total score ranged from 0 (worst) to 36 (best), where higher scores correspond to better outcomes. As pre-specified in the protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | Quality of Life (QoL) analysis set consisted of all participants who had any QoL data. Here "overall number of participants analyzed" are the participants who were evaluable for the outcome measure and "number analyzed" were the participants who were evaluable at given time points. | Posted | Mean | Standard Deviation | score on a scale | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
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| Secondary | HRQoL Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Scores | The EORT QLQ-C30 consisted of 30 questions comprising 9 multiple-item scales and 6 single items. Multiple-item scales of QLQ-C30 consisted of 5 functional scales (physical, role, emotional, cognitive, and social) and 3 symptom scales (fatigue, nausea and vomiting, pain) and a global health status/QOL score. Six single-item scales of QLQ-C30 involved dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties. First 28 questions used a 4-point scale (1 = Not at all to 4 = Very much); and last 2 questions used a 7-point scale (1 = Very poor to 7 = Excellent). Scores for all scales range from 0 to 100. For the overall HRQoL and functioning scales, a higher score was correlated with better HRQoL, whereas a higher score for symptom scales represented worse HRQoL. As pre-specified in protocol, data for secondary outcome measure was collected and analyzed till primary analysis only. | QoL analysis set consisted of all participants who had any QoL data. Here, overall number of participants analyzed" are the participants who were evaluable for the outcome measure and "number analyzed" were the participants who were evaluable at given time points. | Posted | Mean | Standard Deviation | score on a scale | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
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| Secondary | HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS) | The EQ-5D-3L is a health profile questionnaire assessing quality of life along 5 dimensions. Participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. The EQ-5D index was calculated by applying preference-based weights (tariffs) to the scores of the five health state dimensions. Index values can range from -1 to 1, with 0 representing a health state equivalent to death and 1 representing perfect health. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). | QoL analysis set consisted of all participants who had any QoL data. Here "overall number of participants analyzed" are the participants who were evaluable for the outcome measure and "number analyzed" were the participants who were evaluable at given time points. . As pre-specified in protocol, data for this secondary outcome measure was collected and analyzed till primary analysis only. | Posted | Mean | Standard Deviation | score on a scale | At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length =28 days), and at the Off-treatment visit (up to 29 months) |
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| Secondary | Progression-free Survival After Next Line of Therapy (PFS2) | PFS2, defined as the time from randomization to the date of PD after next line of therapy or death from any cause, whichever occurred first based on investigator assessment according to RECIST v1.1. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Median PFS2 was analyzed using the Kaplan-Meier product-limit estimates for each treatment group and presented with 2-sided 95% CI. As pre-specified in protocol, data for this secondary outcome measure was collected and analyzed till the primary analysis only. | PPAS1 included all randomized participants minus the 32 participants who had received >=2 incorrect lenvatinib doses due to IxRS issues. | Posted | Median | 95% Confidence Interval | months | From the time of randomization to the date of PD after next line of therapy or death from any cause or the date of data cutoff for the primary analysis, whichever occurs first (up to 29 months) |
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From date of first dose of study drug up to 28 days after last dose of study drug (up to 71 months)
Reported deaths included all anticipated and unanticipated deaths due to any cause in the study.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lenvatinib 14 mg + Everolimus 5 mg | Participants received lenvatinib 14 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose for in a 28-day treatment cycle until progressive disease (PD), development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. If there were no intolerable Grade 2 or any >= Grade 3 TEAEs that required dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), lenvatinib dose was escalated to 18 mg once daily (along with everolimus 5 mg) beginning in Cycle 2 or later (cycle length = 28 days) during randomization phase. | 71 | 173 | 92 | 173 | 172 | 173 |
| EG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose for in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. | 60 | 168 | 87 | 168 | 166 | 168 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
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| Splenic vein thrombosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Cardiopulmonary failure | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Cardiovascular disorder | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
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| Adrenal insufficiency | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
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| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
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| Blindness | Eye disorders | MedDRA (23.0) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Anal fistula | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Enterocolitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Gastric ulcer | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Gastric ulcer perforation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Death | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Multiple organ dysfunction syndrome | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gallbladder obstruction | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant biliary obstruction | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Anal abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Appendiceal abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Appendicitis perforated | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis infective | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Chronic sinusitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Empyema | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Encephalitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Intestinal sepsis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Large intestine infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Liver abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Lung abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Lymphangitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Paracancerous pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Perihepatic abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Perineal abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia fungal | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Viral diarrhoea | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Subdural haemorrhage | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Troponin increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fluid overload | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Cholangiocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Pericardial effusion malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Tumour necrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Tumour obstruction | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Intraventricular haemorrhage | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Calculus bladder | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nephropathy toxic | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hydrothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary cavitation | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute febrile neutrophilic dermatosis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Aortic thrombosis | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypovolaemic shock | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Peripheral venous disease | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Faeces hard | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholangitis acute | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Haematoma muscle | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rib deformity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cancer fatigue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Metastatic renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Oncologic complication | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Livedo reticularis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Peripheral artery occlusion | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | 1-888-274-2378 | esi_oncmedinfo@eisai.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 29, 2020 | Jan 28, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C531958 | lenvatinib |
| D000068338 | Everolimus |
| ID | Term |
|---|---|
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
|
|
|
| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
|
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first.
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants with RCC received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up or until the end of the study, whichever occurred first in studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and in this current study E7080-G000-218 (NCT03173560). |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants with RCC received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up or until the end of the study, whichever occurred first in studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) and in this current study E7080-G000-218 (NCT03173560). |
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| OG001 | Lenvatinib + Everolimus 5 mg | Participants with RCC received lenvatinib 12 to 24 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up or until the end of the study, whichever occurred first in studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or in this current study E7080-G000-218 (NCT03173560). |
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| OG001 | Lenvatinib + Everolimus 5 mg | Participants with RCC received lenvatinib 12 to 24 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up or until the end of the study, whichever occurred first in studies E7080-G000-205 (NCT01136733), E7080-M001-221 (NCT02915783), E7080-J081-112 (NCT02454478) or in this current study E7080-G000-218 (NCT03173560). |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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Participants received lenvatinib 14 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. Participants who had no intolerable Grade 2 or any >=Grade 3 TEAEs that required dose reduction in the first 28-day cycle (that is, the first 4 weeks of treatment), had lenvatinib dose titrated to 18 mg once daily (along with everolimus 5 mg) beginning in Cycle 2 or later (cycle length =28 days) during randomization phase. |
| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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| OG001 | Lenvatinib 18 mg + Everolimus 5 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily along with everolimus 5 mg, tablet, orally, once daily as the starting dose in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first. |
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