Back to resultsA Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Lenvatinib
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring Unresectable advanced or metastatic renal cell carcinoma
Eligibility Criteria
Select Inclusion Criteria:
- Histologically confirmed diagnosis of renal cell carcinoma.
- Phase 2: Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable).
- Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.
- Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
Select Exclusion Criteria:
Phase 1b or Phase 2 specific per below:
- Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.
- Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.
Phase 1b or Phase 2 specific per below:
- Phase 1b only: Prior exposure to lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
- Subjects should not have received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anticancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
- Subjects having greater than 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
- Subjects with urine protein greater than or equal to 1 g/24 hours will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 1.5 x ULN.
- Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
- Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
- Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
Lenvatinib
Lenvatinib plus Everolimus
Everolimus
Arm Description
Outcomes
Primary Outcome Measures
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
A DLT was defined as either a treatment-related failure to administer greater than or equal to (>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) >= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 (RP2) Dose
The highest dose level resulting in 0 or 1 DLT in 6 participants was to be considered the MTD of Phase 1b. Once the MTD was established, the participant cohort was expanded to a minimum of 10 participants. The MTD was confirmed by assessing DLTs during Cycle 1 and intolerable toxicities (i.e., not manageable with dose interruption and/or reduction) during Cycle 2 of therapy. Once the dose of lenvatinib/everolimus combination to be used in the succeeding Phase 2 part of the study was established, enrollment into Phase 2 was started. The RP2 dose was the same as the confirmed MTD and was used for the Phase 2 Treatment Arm A of this study.
Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
Secondary Outcome Measures
Phase 2: Overall Survival (OS)
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.
Phase 2: Objective Response Rate (ORR)
The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions. Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease). The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a BOR of CR or PR or SD (minimum duration from randomization to SD greater than or equal to 7 weeks). Assessments were performed every 8 weeks and were based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD greater than or equal to 7 weeks.
Durable Stable Disease (SD) Rate
The durable SD rate was defined as the percentage of participants whose BOR was SD and the duration of SD was greater than or equal to 23 weeks. The durable SD was based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson.
Clinical Benefit Rate (CBR)
The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (duration of SD was greater than or equal to 23 weeks) and was based on investigator review data using RECIST 1.1. The BOR was defined as the best response recorded from the start of study treatment until discontinuation from the study. There was no requirement for confirmatory measurement of PR or CR to deem either one the BOR. The 95% CI was constructed using the method of Clopper and Pearson. CBR = CR + PR + SD greater than or equal to 23 weeks.
Summary of Plasma Concentrations of Lenvatinib for Sparse Pharmacokinetic (PK) Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Plasma concentrations of lenvatinib were measured and concentration data were summarized. The summary statistics at time points with one or more below the limit of quantitation (BLQ) values were calculated by assigning zero for each BLQ value.
Summary of Blood Concentrations of Everolimus for Sparse PK Sampling for Phase 1b and Phase 2
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Whole blood concentrations of everolimus were measured and concentration data were summarized. The summary statistics at time points with one or more BLQ values were calculated by assigning zero for each BLQ value.
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC(0-24)) for Lenvatinib When Administered Alone or in Combination With Everolimus
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for lenvatinib were derived from lenvatinib concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Maximum Concentration (Cmax) of Lenvatinib in Plasma When Administered Alone or in Combination With Everolimus
Cmax for lenvatinib was defined as the maximum observed concentration of lenvatinib in plasma following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured plasma concentration-time curves.
Time to Cmax (Tmax) for Lenvatinib When Administered Alone or in Combination With Everolimus
Tmax for lenvatinib was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach maximum concentration (Cmax) of lenvatinib in plasma.
Area Under the Blood Concentration-Time Curve From 0 to 24 Hours for Everolimus When Administered Alone or in Combination With Lenvatinib
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for everolimus were derived from everolimus concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Maximum Concentration of Everolimus (Cmax) in Blood When Administered Alone or in Combination With Lenvatinib
Cmax for everolimus was defined as the maximum observed concentration of everolimus in blood following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured blood concentration-time curves.
Time to Cmax (Tmax) for Everolimus When Administered Alone or in Combination With Lenvatinib
Tmax for everolimus was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach the maximum concentration (Cmax) of everolimus in blood.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01136733
Brief Title
A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment
Official Title
An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
August 5, 2010 (Actual)
Primary Completion Date
June 13, 2014 (Actual)
Study Completion Date
February 8, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
5. Study Description
Brief Summary
This is an open-label, multicenter, Phase 1b/2 study of lenvatinib alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
Unresectable advanced or metastatic renal cell carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
173 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenvatinib
Arm Type
Experimental
Arm Title
Lenvatinib plus Everolimus
Arm Type
Experimental
Arm Title
Everolimus
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
E7080, Lenvima, Kisplyx
Intervention Description
taken orally, once a day
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
taken orally, once a day
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Dose-limiting Toxicity (DLT)
Description
A DLT was defined as either a treatment-related failure to administer greater than or equal to (>=) 75% of the planned dosage of lenvatinib/everolimus or a specific National Cancer Institute Common Toxicity Criteria (NCI CTC) >= Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care daily living activities) hematologic or nonhematologic toxicities considered to be possibly related to lenvatinib and/or everolimus therapy assessed during the first treatment cycle of each dose level. Higher grade indicates more severe toxicity.
Time Frame
First dose of study drug (Cycle 1 Day 1) to end of first 4 weeks of therapy (Cycle 1)
Title
Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 (RP2) Dose
Description
The highest dose level resulting in 0 or 1 DLT in 6 participants was to be considered the MTD of Phase 1b. Once the MTD was established, the participant cohort was expanded to a minimum of 10 participants. The MTD was confirmed by assessing DLTs during Cycle 1 and intolerable toxicities (i.e., not manageable with dose interruption and/or reduction) during Cycle 2 of therapy. Once the dose of lenvatinib/everolimus combination to be used in the succeeding Phase 2 part of the study was established, enrollment into Phase 2 was started. The RP2 dose was the same as the confirmed MTD and was used for the Phase 2 Treatment Arm A of this study.
Time Frame
First dose of study drug (Cycle 1 Day 1) to end of Cycle 2 (1 cycle = 28 days/4 weeks)
Title
Phase 2: Progression-Free Survival (PFS)
Description
PFS was defined as the time (in months) from the date of first dose of study drug to the first documentation of disease progression or death, whichever occurred first. Kaplan-Meier (K-M) estimates were used to estimate median PFS, presented with 2-sided 95% confidence intervals (CIs). Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease using computed tomography (CT) or magnetic resonance imaging (MRI) and scan acquisition techniques (including use or nonuse of intravenous (IV) contrast). Tumor response was determined at the site by the investigator and radiologist using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 in the evaluation of the tumor assessment scans. The date of objective disease progression was defined as the earliest date of radiological disease progression. Participants removed from therapy due to clinical progression with no radiologic confirmation were censored at their last radiologic assessment date.
Time Frame
Date of randomization into Phase 2 (Cycle 1 Day 1) to the date of first documentation of disease progression or death (whichever occurred first), assessed up to data cutoff date (13 Jun 2014), up to approximately 2 years and 3 months
Secondary Outcome Measure Information:
Title
Phase 2: Overall Survival (OS)
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.
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: Objective Response Rate (ORR)
Description
The ORR was defined as the percentage of participants who had the best overall response (BOR) of complete response (CR) or partial response (PR) as determined by the investigator, using RECIST 1.1 in the evaluation of MRI or CT scans of targeted lesions. Tumor assessments were performed every 8 weeks (or sooner if there was evidence of progressive disease). The BOR was defined as the best response recorded from the start of the study treatment until discontinuation from the study. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR was calculated with exact 95% CIs using the method of Clopper and Pearson.
Time Frame
Randomization (Cycle 1 Day 1) until first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Title
Disease Control Rate (DCR)
Description
The DCR was defined as the percentage of participants who had a BOR of CR or PR or SD (minimum duration from randomization to SD greater than or equal to 7 weeks). Assessments were performed every 8 weeks and were based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson. DCR = CR + PR + SD greater than or equal to 7 weeks.
Time Frame
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Title
Durable Stable Disease (SD) Rate
Description
The durable SD rate was defined as the percentage of participants whose BOR was SD and the duration of SD was greater than or equal to 23 weeks. The durable SD was based on investigator review data using RECIST 1.1. The 95% CI was constructed using the method of Clopper and Pearson.
Time Frame
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Title
Clinical Benefit Rate (CBR)
Description
The CBR was defined as the percentage of participants who had BOR of CR, PR, or durable SD (duration of SD was greater than or equal to 23 weeks) and was based on investigator review data using RECIST 1.1. The BOR was defined as the best response recorded from the start of study treatment until discontinuation from the study. There was no requirement for confirmatory measurement of PR or CR to deem either one the BOR. The 95% CI was constructed using the method of Clopper and Pearson. CBR = CR + PR + SD greater than or equal to 23 weeks.
Time Frame
Baseline (Randomization) to first evidence of disease progression, assessed up to the data cutoff date (13 Jun 2014), or up to approximately 2 years and 3 months
Title
Summary of Plasma Concentrations of Lenvatinib for Sparse Pharmacokinetic (PK) Sampling for Phase 1b and Phase 2
Description
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Plasma concentrations of lenvatinib were measured and concentration data were summarized. The summary statistics at time points with one or more below the limit of quantitation (BLQ) values were calculated by assigning zero for each BLQ value.
Time Frame
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
Title
Summary of Blood Concentrations of Everolimus for Sparse PK Sampling for Phase 1b and Phase 2
Description
Blood samples were collected during the Randomization Phase. Most participants had 6 samples taken over 3 cycles of treatment (sparse sampling - 2 samples taken per cycle, one at predose and one at 2 to 8 hours postdose). Whole blood concentrations of everolimus were measured and concentration data were summarized. The summary statistics at time points with one or more BLQ values were calculated by assigning zero for each BLQ value.
Time Frame
Cycle 1 (Day 1), Cycle 2 (Day 1), Cycle 3 (Day 1)
Title
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC(0-24)) for Lenvatinib When Administered Alone or in Combination With Everolimus
Description
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for lenvatinib were derived from lenvatinib concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Time Frame
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
Title
Maximum Concentration (Cmax) of Lenvatinib in Plasma When Administered Alone or in Combination With Everolimus
Description
Cmax for lenvatinib was defined as the maximum observed concentration of lenvatinib in plasma following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured plasma concentration-time curves.
Time Frame
Phase 2: Cycle 1 Day 15
Title
Time to Cmax (Tmax) for Lenvatinib When Administered Alone or in Combination With Everolimus
Description
Tmax for lenvatinib was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach maximum concentration (Cmax) of lenvatinib in plasma.
Time Frame
Phase 2: Cycle 1 Day 15
Title
Area Under the Blood Concentration-Time Curve From 0 to 24 Hours for Everolimus When Administered Alone or in Combination With Lenvatinib
Description
Between 9 and 12 participants in each of the 3 treatment arms participated in an optional substudy where instead of the sparse sampling, 9 samples were to be taken over 1 single 24-hour period (i.e., intensive sampling) for full PK profiling. Blood samples were analyzed for study drug using standardized methods. PK parameters for everolimus were derived from everolimus concentration data using non-compartmental methods. Data were compared via descriptive statistics between single agent and combination therapy.
Time Frame
Phase 2: Cycle 1 Day 15 immediately predose, and 30 minutes, 1, 2, 3, 4, 8, 12 (optional), and 24 hours postdose (predose on Day 16)
Title
Maximum Concentration of Everolimus (Cmax) in Blood When Administered Alone or in Combination With Lenvatinib
Description
Cmax for everolimus was defined as the maximum observed concentration of everolimus in blood following administration of study treatment on Cycle 1 Day 15 and was obtained directly from the measured blood concentration-time curves.
Time Frame
Phase 2: Cycle 1 Day 15
Title
Time to Cmax (Tmax) for Everolimus When Administered Alone or in Combination With Lenvatinib
Description
Tmax for everolimus was the amount of time taken after administration of study treatment on Cycle 1 Day 15 to reach the maximum concentration (Cmax) of everolimus in blood.
Time Frame
Phase 2: Cycle 1 Day 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Select Inclusion Criteria:
Histologically confirmed diagnosis of renal cell carcinoma.
Phase 2: Histological or cytological confirmation of predominant clear cell renal cell carcinoma (RCC) (original tissue diagnosis of RCC is acceptable).
Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC.
Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
Select Exclusion Criteria:
Phase 1b or Phase 2 specific per below:
Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded.
Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.
Phase 1b or Phase 2 specific per below:
Phase 1b only: Prior exposure to lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
Subjects should not have received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anticancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
Subjects having greater than 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Subjects with urine protein greater than or equal to 1 g/24 hours will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 1.5 x ULN.
Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eisai Medical Services
Organizational Affiliation
Eisai Limited
Official's Role
Study Director
Facility Information:
City
Tucson
State/Province
Arizona
Country
United States
City
Orange
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Joliet
State/Province
Illinois
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Annapolis
State/Province
Maryland
Country
United States
City
Bethesda
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Tupelo
State/Province
Mississippi
Country
United States
City
New York
State/Province
New York
Country
United States
City
Tulsa
State/Province
Oklahoma
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Brno
Country
Czechia
City
Olomouc
Country
Czechia
City
Prague
Country
Czechia
City
Gdansk
Country
Poland
City
Lodz
Country
Poland
City
Szczecin
Country
Poland
City
Warsaw
Country
Poland
City
Barcelona
Country
Spain
City
Cordoba
Country
Spain
City
Madrid
Country
Spain
City
Pamplona
Country
Spain
City
Bristol
Country
United Kingdom
City
Cambridge
Country
United Kingdom
City
Cardiff
Country
United Kingdom
City
Glasgow
Country
United Kingdom
City
Guildford
Country
United Kingdom
City
Ipswich
Country
United Kingdom
City
Leicester
Country
United Kingdom
City
London
Country
United Kingdom
City
Manchester
Country
United Kingdom
City
Southampton
Country
United Kingdom
City
Surrey
Country
United Kingdom
City
Wirral
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33024271
Citation
Lee CH, Motzer RJ, Glen H, Michaelson MD, Larkin J, Minoshima Y, Kanekiyo M, Ikezawa H, Sachdev P, Dutcus CE, Funahashi Y, Voss MH. Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma. Br J Cancer. 2021 Jan;124(1):237-246. doi: 10.1038/s41416-020-01092-0. Epub 2020 Oct 7.
Results Reference
derived
PubMed Identifier
26482279
Citation
Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22. Erratum In: Lancet Oncol. 2016 Jul;17 (7):e270. Lancet Oncol. 2018 Oct;19(10):e509.
Results Reference
derived
Learn more about this trial
A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment
We'll reach out to this number within 24 hrs