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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03173560




Registration number
NCT03173560
Ethics application status
Date submitted
22/05/2017
Date registered
2/06/2017

Titles & IDs
Public title
Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. 14 mg) in Combination With Everolimus in Participants With Renal Cell Carcinoma
Scientific title
A Randomized, Open-Label (Formerly Double-Blind), Phase 2 Trial to Assess Safety and Efficacy of Lenvatinib at Two Different Starting Doses (18 mg vs. 14 mg QD) in Combination With Everolimus (5 mg QD) in Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
Secondary ID [1] 0 0
2016-002778-11
Secondary ID [2] 0 0
E7080-G000-218
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lenvatinib
Treatment: Drugs - everolimus

Experimental: Lenvatinib 14 mg plus everolimus 5 mg - 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.

Experimental: Lenvatinib 18 mg plus everolimus 5 mg - 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.


Treatment: Drugs: lenvatinib
lenvatinib capsules.

Treatment: Drugs: everolimus
everolimus tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate at Week 24 (ORR24W)
Timepoint [1] 0 0
At Week 24
Primary outcome [2] 0 0
Percentage of Participants With Intolerable Grade 2 or Any Grade >=Grade 3 TEAEs Within 24 Weeks
Timepoint [2] 0 0
Up to Week 24
Secondary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Number of Participants With TEAEs and Serious TEAEs
Timepoint [3] 0 0
From date of first dose of study drug up to 28 days after last dose of study drug, or date of data cut off for the primary analysis (up to 29 months)
Secondary outcome [4] 0 0
Percentage of Participants Who Discontinued Treatment Due to Toxicity
Timepoint [4] 0 0
From date of first dose of study drug up to 28 days after last dose of study drug, or date of data cut off for the primary analysis (up to 29 months)
Secondary outcome [5] 0 0
Time to Treatment Failure Due to Toxicity
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Health-Related Quality of Life (HRQoL) Assessed by Functional Assessment of Cancer Therapy Kidney Syndrome Index-Disease-Related Symptoms (FKSI-DRS) Scores
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
HRQoL Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Scores
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
HRQoL Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS)
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Progression-free Survival After Next Line of Therapy (PFS2)
Timepoint [10] 0 0
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)

Eligibility
Key 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:

* Lymph node (LN) lesion that measures at least 1 dimension as >=1.5 centimeter (cm) in the short axis;
* Non-nodal lesion that measures >=1.0 cm in the longest diameter;
* The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.
* 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:

* Absolute neutrophil count (ANC) >=1500/millimeters cubed (mm^3) (>=1.5*10^9/Liters [L]);
* Platelets >=100,000/mm^3 (>=100*10^9/L);
* Hemoglobin >=9 grams per deciliter (g/dL)
* 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:

* Total bilirubin <=1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome;
* Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <=3* the ULN (in the case of liver metastases <=5* the ULN). Participants with bone metastases with ALP values greater than 3 times can be included.
* Participant must voluntarily agree to provide written informed consent
* Participant must be willing and able to comply with all aspects of the protocol
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 International Units per Liter [IU/L] or equivalent units of ß-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:

* total abstinence (if it is their preferred and usual lifestyle)
* an intrauterine device (IUD) or hormone releasing system (IUS)
* a contraceptive implant
* an oral contraceptive (with additional barrier method) (Note: Participants must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study.) OR
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2024
Actual
Sample size
Target
Accrual to date
Final
343
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University - Macquarie Park
Recruitment hospital [2] 0 0
Northern Cancer Institute, Saint Leonards - Saint Leonards
Recruitment hospital [3] 0 0
Adelaide Cancer Center - Kurralta Park
Recruitment hospital [4] 0 0
Sunshine Hospital - Saint Albans
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment postcode(s) [2] 0 0
- Saint Leonards
Recruitment postcode(s) [3] 0 0
- Kurralta Park
Recruitment postcode(s) [4] 0 0
- Saint Albans
Recruitment postcode(s) [5] 0 0
- Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Hawaii
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Czechia
State/province [12] 0 0
Brno
Country [13] 0 0
Czechia
State/province [13] 0 0
Olomouc
Country [14] 0 0
Czechia
State/province [14] 0 0
Prague
Country [15] 0 0
Finland
State/province [15] 0 0
Helsinki
Country [16] 0 0
Finland
State/province [16] 0 0
Tampere
Country [17] 0 0
Finland
State/province [17] 0 0
Turku
Country [18] 0 0
Finland
State/province [18] 0 0
Vaasa
Country [19] 0 0
Greece
State/province [19] 0 0
Athens
Country [20] 0 0
Greece
State/province [20] 0 0
Patras
Country [21] 0 0
Greece
State/province [21] 0 0
Pylaia
Country [22] 0 0
Greece
State/province [22] 0 0
Thessaloniki
Country [23] 0 0
Italy
State/province [23] 0 0
Lombardia
Country [24] 0 0
Italy
State/province [24] 0 0
Arezzo
Country [25] 0 0
Italy
State/province [25] 0 0
Napoli
Country [26] 0 0
Italy
State/province [26] 0 0
Roma
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Gyeonggido
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Chonam
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seoul
Country [30] 0 0
Netherlands
State/province [30] 0 0
Den Haag
Country [31] 0 0
Netherlands
State/province [31] 0 0
Leiden
Country [32] 0 0
Poland
State/province [32] 0 0
Brzozow
Country [33] 0 0
Poland
State/province [33] 0 0
Gdansk
Country [34] 0 0
Poland
State/province [34] 0 0
Krakow
Country [35] 0 0
Poland
State/province [35] 0 0
Lublin
Country [36] 0 0
Poland
State/province [36] 0 0
Opole
Country [37] 0 0
Poland
State/province [37] 0 0
Rzeszow
Country [38] 0 0
Poland
State/province [38] 0 0
Warszawa
Country [39] 0 0
Portugal
State/province [39] 0 0
Coimbra
Country [40] 0 0
Portugal
State/province [40] 0 0
Lisboa
Country [41] 0 0
Portugal
State/province [41] 0 0
Lisbon
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Romania
State/province [43] 0 0
Cluj-Napoca
Country [44] 0 0
Romania
State/province [44] 0 0
Craiova
Country [45] 0 0
Romania
State/province [45] 0 0
Timisoara
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Barnaul
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Chelyabinsk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Obninsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Omsk
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Yaroslavl
Country [52] 0 0
Spain
State/province [52] 0 0
A Coruna
Country [53] 0 0
Spain
State/province [53] 0 0
Badalona
Country [54] 0 0
Spain
State/province [54] 0 0
Barcelona
Country [55] 0 0
Spain
State/province [55] 0 0
Cordoba
Country [56] 0 0
Spain
State/province [56] 0 0
Hospitalet de Llobregat
Country [57] 0 0
Spain
State/province [57] 0 0
Madrid
Country [58] 0 0
Spain
State/province [58] 0 0
Palma de Mallorca
Country [59] 0 0
Spain
State/province [59] 0 0
Pamplona
Country [60] 0 0
Spain
State/province [60] 0 0
Valencia
Country [61] 0 0
Taiwan
State/province [61] 0 0
Taichung
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taipei
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Glasgow
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Manchester
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Northwood
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03173560