{"analyses":[{"ciLowerLimit":"0.299","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"0.884","estimateComment":"Hazard ratio between treatment groups and corresponding 95% CI was estimated using the stratified Cox regression model (stratified by hemoglobin and corrected serum calcium) with treatment as a factor.","groupDescription":"Planned analyses were performed to test null hypothesis of treatment difference in OS at a nominal significance level of 0.05 (2-sided) using the stratified log-rank test using stratification factors.","groupIds":["OG004","OG006"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"=0.0242","paramType":"Hazard Ratio (HR)","paramValue":"0.514","statisticalMethod":"Log Rank"},{"ciLowerLimit":"0.411","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"1.138","groupIds":["OG005","OG006"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"=0.1181","paramType":"Hazard Ratio (HR)","paramValue":"0.684","statisticalMethod":"Log Rank"},{"ciLowerLimit":"0.433","ciNumSides":"TWO_SIDED","ciPctValue":"95","ciUpperLimit":"1.301","groupIds":["OG004","OG005"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"=0.3157","paramType":"Hazard Ratio (HR)","paramValue":"0.751","statisticalMethod":"Log Rank"}],"classes":[{"categories":[{"measurements":[{"comment":"NA = not estimable","groupId":"OG004","lowerLimit":"16.4","upperLimit":"NA","value":"25.5"},{"groupId":"OG005","lowerLimit":"13.6","upperLimit":"26.2","value":"19.1"},{"groupId":"OG006","lowerLimit":"11.8","upperLimit":"19.6","value":"15.4"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"},{"groupId":"OG004","value":"51"},{"groupId":"OG005","value":"52"},{"groupId":"OG006","value":"50"}],"units":"Participants"}],"description":"OS was defined as the time (in months) from the date of randomization until date of death from any cause. Median survival time was calculated using K-M estimate for each treatment arm and presented with 2-sided 95% CIs. Participants who were lost to follow-up or alive at the data cutoff date (10 Dec 2014) were censored at the date the participants were last known to be alive.","dispersionType":"95% Confidence Interval","groups":[{"description":"Oral lenvatinib (12 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in a fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no dose-limiting toxicity (DLT) occurred, then enrollment proceeded to Cohort 2. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 1. If 1 or none of the 6 participants had a DLT, then enrollment proceeded to Cohort 2.\n\nIf 2 or more participants had a DLT during Cycle 1, the dose escalation committee (DEC) decided if they were lenvatinib-related and if enrollment could proceed, lenvatinib was reduced to 6 mg daily (everolimus dose was not reduced). If it could not be determined that the DLTs were lenvatinib-related, enrollment stopped.","id":"OG000","title":"Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment would proceed to Cohort 3. If 1 participant had a DLT, 3 more participants were enrolled in Cohort 2. If 1 or none of the 6 participants exhibited a DLT, enrollment proceeded to Cohort 3.\n\nIf 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.","id":"OG001","title":"Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (24 mg) and everolimus (5 mg) were taken once daily in continuous 28-day cycles. Dose Escalation Cohort-Cycle 1: both study drugs were taken at the same time of day in the fasting state with water. Cycles 2, 3, etc. and Expansion Cohort: both study drugs were taken at the same time of day with water, either after a meal or in a fasting state. Dose escalation began with 3 participants in Cohort 1. If no DLT occurred, then enrollment proceeded to Cohort 4. If 1 participant had a DLT, 3 more participants were enrolled Cohort 3. If 1 or none of the 6 participants exhibited a DLT, then enrollment proceeded to Cohort 4.\n\nIf 2 or more participants had a DLT during Cycle 1, dose escalation ceased and additional participants were enrolled to the next lower dose to achieve a total of 6 participants in that cohort.","id":"OG002","title":"Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"The DLT was achieved and no participants were enrolled into this cohort.","id":"OG003","title":"Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus"},{"description":"Oral lenvatinib (18 mg) and everolimus (5 mg) were taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles. Treatment cycles began with the first dose of study drug in Cycle 1 and continued in 28-day (4-week) consecutive cycles until completion of the off-treatment assessments (within 30 days after the last study treatment administration). Study drugs were administered at the clinic for the first dose and on the pharmacokinetic (PK) sampling days.","id":"OG004","title":"Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus"},{"description":"Oral lenvatinib (24 mg) was taken once daily in the morning (consistently with or without food) with water, in continuous 28-day (4-week) cycles.","id":"OG005","title":"Phase 2 (Arm B): 24 mg Lenvatinib"},{"description":"Oral everolimus (10 mg) was taken once daily in the morning (consistently either with or without food) with water, in continuous 28-day (4-week) cycles.","id":"OG006","title":"Phase 2 (Arm C): 10 mg Everolimus"}],"paramType":"MEDIAN","populationDescription":"Full analysis set which included all randomized participants.","reportingStatus":"POSTED","timeFrame":"Randomization (Cycle 1 Day 1) until date of death from any cause, assessed up to the data cutoff date (10 Dec 2014), up to approximately 2 years and 9 months","title":"Phase 2: Overall Survival (OS)","type":"SECONDARY","unitOfMeasure":"Months"}