TriangleNCT01136733 · OUTCOME
Phase 2: Overall Survival (OS)
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEDIAN
- Unit
- Months
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- 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
What was measured
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.
Analysis population: Full analysis set which included all randomized participants.
Groups in this outcome
Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus
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. If 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.
Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus
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. If 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.
Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus
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. If 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.
Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus
The DLT was achieved and no participants were enrolled into this cohort.
Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus
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.
Phase 2 (Arm B): 24 mg Lenvatinib
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.
Phase 2 (Arm C): 10 mg Everolimus
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.
| Group | Source count |
|---|---|
| Phase 1b (Cohort 1): 12 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 2): 18 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 3): 24 mg Lenvatinib Plus 5 mg Everolimus | 0 |
| Phase 1b (Cohort 4): 24 mg Lenvatinib Plus 10 mg Everolimus | 0 |
| Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus | 51 |
| Phase 2 (Arm B): 24 mg Lenvatinib | 52 |
| Phase 2 (Arm C): 10 mg Everolimus | 50 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Phase 2 (Arm A): 18 mg Lenvatinib Plus 5 mg Everolimus | 25.5 | Not reported | 16.4 | NA | NA = not estimable |
| Phase 2 (Arm B): 24 mg Lenvatinib | 19.1 | Not reported | 13.6 | 26.2 | Not reported |
| Phase 2 (Arm C): 10 mg Everolimus | 15.4 | Not reported | 11.8 | 19.6 | Not reported |
Source statistical analyses
- ci Lower Limit
- 0.299
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.884
- estimate Comment
- 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.
- group Description
- 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.
- group Ids
- OG004
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.0242
- param Type
- Hazard Ratio (HR)
- param Value
- 0.514
- statistical Method
- Log Rank
- ci Lower Limit
- 0.411
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.138
- group Ids
- OG005
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.1181
- param Type
- Hazard Ratio (HR)
- param Value
- 0.684
- statistical Method
- Log Rank
- ci Lower Limit
- 0.433
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.301
- group Ids
- OG004
- OG005
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.3157
- param Type
- Hazard Ratio (HR)
- param Value
- 0.751
- statistical Method
- Log Rank
Complete source fields
- analyses
- ci Lower Limit
- 0.299
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.884
- estimate Comment
- 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.
- group Description
- 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.
- group Ids
- OG004
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.0242
- param Type
- Hazard Ratio (HR)
- param Value
- 0.514
- statistical Method
- Log Rank
- ci Lower Limit
- 0.411
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.138
- group Ids
- OG005
- OG006
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.1181
- param Type
- Hazard Ratio (HR)
- param Value
- 0.684
- statistical Method
- Log Rank
- ci Lower Limit
- 0.433
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 1.301
- group Ids
- OG004
- OG005
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- =0.3157
- param Type
- Hazard Ratio (HR)
- param Value
- 0.751
- statistical Method
- Log Rank
- classes
- categories
- measurements
- comment
- NA = not estimable
- group Id
- OG004
- lower Limit
- 16.4
- upper Limit
- NA
- value
- 25.5
- group Id
- OG005
- lower Limit
- 13.6
- upper Limit
- 26.2
- value
- 19.1
- group Id
- OG006
- lower Limit
- 11.8
- upper Limit
- 19.6
- value
- 15.4
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- group Id
- OG002
- value
- 0
- group Id
- OG003
- value
- 0
- group Id
- OG004
- value
- 51
- group Id
- OG005
- value
- 52
- group Id
- 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.
- dispersion Type
- 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. If 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. If 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. If 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
- param Type
- MEDIAN
- population Description
- Full analysis set which included all randomized participants.
- reporting Status
- POSTED
- time Frame
- 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
- unit Of Measure
- Months
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Preserved source evidence · Not medical advice