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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03713593




Registration number
NCT03713593
Ethics application status
Date submitted
18/10/2018
Date registered
22/10/2018

Titles & IDs
Public title
Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)
Scientific title
A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib in First-line Therapy of Participants With Advanced Hepatocellular Carcinoma (LEAP-002)
Secondary ID [1] 0 0
MK-7902-002
Secondary ID [2] 0 0
7902-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lenvatinib
Treatment: Other - pembrolizumab
Treatment: Drugs - saline placebo

Experimental: lenvatinib plus pembrolizumab - Participants receive lenvatinib 12 mg (for participants with screening body weight =60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.

Active comparator: lenvatinib plus placebo - Participants receive lenvatinib 12 mg (for participants with screening body weight =60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.


Treatment: Drugs: lenvatinib
Administered orally once a day

Treatment: Other: pembrolizumab
Administered as an IV infusion on Day 1 Q3W

Treatment: Drugs: saline placebo
Administered as an IV infusion on Day 1 Q3W
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 41 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 41 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to approximately 41 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [2] 0 0
Up to approximately 41 months
Secondary outcome [3] 0 0
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [3] 0 0
Up to approximately 41 months
Secondary outcome [4] 0 0
Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [4] 0 0
Up to approximately 41 months
Secondary outcome [5] 0 0
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [5] 0 0
Up to approximately 41 months
Secondary outcome [6] 0 0
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [6] 0 0
Up to approximately 41 months
Secondary outcome [7] 0 0
Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [7] 0 0
Up to approximately 41 months
Secondary outcome [8] 0 0
Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [8] 0 0
Up to approximately 41 months
Secondary outcome [9] 0 0
Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [9] 0 0
Up to approximately 41 months
Secondary outcome [10] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [10] 0 0
Up to approximately 41 months
Secondary outcome [11] 0 0
Number of Participants Who Experienced an Serious Adverse Event (SAE)
Timepoint [11] 0 0
Up to approximately 41 months
Secondary outcome [12] 0 0
Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest
Timepoint [12] 0 0
Up to approximately 41 months
Secondary outcome [13] 0 0
Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI)
Timepoint [13] 0 0
Up to approximately 41 months
Secondary outcome [14] 0 0
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Timepoint [14] 0 0
Up to approximately 41 months

Eligibility
Key inclusion criteria
* Is male or female and =18 years of age at the time of signing the informed consent
* Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
* Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
* Has a Child-Pugh class A liver score
* Has a predicted life expectancy of >3 months
* Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR
* Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
* Participants with hepatitis B will be eligible as long as their virus is well controlled
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has had esophageal or gastric variceal bleeding within the last 6 months
* Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
* Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula
* Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention
* Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
* Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
* Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention
* Has serious non-healing wound, ulcer, or bone fracture
* Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy in the past 3 years
* Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy
* Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator
* Has severe hypersensitivity (=Grade 3) to study intervention and/or any of their excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has urine protein =1 grams/24 hours
* Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected by Fridericia Formula)
* Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
* Has an active infection requiring systemic therapy with the exceptions of hepatitis B virus (HBV) or hepatitis C virus (HCV)
* Has a known history of human immunodeficiency virus (HIV) infection
* Has known active tuberculosis (Bacillus tuberculosis)
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
* Has had an allogenic tissue/solid organ transplant

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/12/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/09/2024
Sample size
Target
Accrual to date
Final
794
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital ( Site 0001) - Camperdown
Recruitment hospital [2] 0 0
Princess Alexandra Hospital ( Site 0007) - Wooloongabba
Recruitment hospital [3] 0 0
Monash Health-Monash Medical Centre ( Site 0004) - Clayton
Recruitment hospital [4] 0 0
St Vincents Hospital Melbourne ( Site 0003) - Fitzroy
Recruitment hospital [5] 0 0
Liverpool Hospital. ( Site 0002) - Liverpool
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
2170 - Liverpool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
Chile
State/province [17] 0 0
Region Del Maule
Country [18] 0 0
Chile
State/province [18] 0 0
Region Metropolitana De Santiago
Country [19] 0 0
Chile
State/province [19] 0 0
Temuco
Country [20] 0 0
China
State/province [20] 0 0
Anhui
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Fujian
Country [23] 0 0
China
State/province [23] 0 0
Guangdong
Country [24] 0 0
China
State/province [24] 0 0
Heilongjiang
Country [25] 0 0
China
State/province [25] 0 0
Hubei
Country [26] 0 0
China
State/province [26] 0 0
Hunan
Country [27] 0 0
China
State/province [27] 0 0
Jiangsu
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
China
State/province [29] 0 0
Shanxi
Country [30] 0 0
China
State/province [30] 0 0
Sichuan
Country [31] 0 0
China
State/province [31] 0 0
Xinjiang
Country [32] 0 0
China
State/province [32] 0 0
Zhejiang
Country [33] 0 0
Colombia
State/province [33] 0 0
Antioquia
Country [34] 0 0
Colombia
State/province [34] 0 0
Atlantico
Country [35] 0 0
Colombia
State/province [35] 0 0
Distrito Capital De Bogota
Country [36] 0 0
Colombia
State/province [36] 0 0
Valle Del Cauca
Country [37] 0 0
France
State/province [37] 0 0
Avignon
Country [38] 0 0
France
State/province [38] 0 0
Clichy
Country [39] 0 0
France
State/province [39] 0 0
Creteil
Country [40] 0 0
France
State/province [40] 0 0
Lille
Country [41] 0 0
France
State/province [41] 0 0
Lyon
Country [42] 0 0
France
State/province [42] 0 0
Marseille
Country [43] 0 0
France
State/province [43] 0 0
Orleans
Country [44] 0 0
France
State/province [44] 0 0
Rennes
Country [45] 0 0
France
State/province [45] 0 0
Vandoeuvre les Nancy
Country [46] 0 0
Germany
State/province [46] 0 0
Aachen
Country [47] 0 0
Germany
State/province [47] 0 0
Dresden
Country [48] 0 0
Germany
State/province [48] 0 0
Essen
Country [49] 0 0
Germany
State/province [49] 0 0
Frankfurt am Main
Country [50] 0 0
Germany
State/province [50] 0 0
Hamburg
Country [51] 0 0
Germany
State/province [51] 0 0
Koeln
Country [52] 0 0
Germany
State/province [52] 0 0
Leipzig
Country [53] 0 0
Germany
State/province [53] 0 0
Magdeburg
Country [54] 0 0
Germany
State/province [54] 0 0
Tuebingen
Country [55] 0 0
Germany
State/province [55] 0 0
Wuerzburg
Country [56] 0 0
Ireland
State/province [56] 0 0
Dublin
Country [57] 0 0
Italy
State/province [57] 0 0
VR
Country [58] 0 0
Italy
State/province [58] 0 0
Aviano
Country [59] 0 0
Italy
State/province [59] 0 0
Bologna
Country [60] 0 0
Italy
State/province [60] 0 0
Padova
Country [61] 0 0
Italy
State/province [61] 0 0
Palermo
Country [62] 0 0
Italy
State/province [62] 0 0
Pavia
Country [63] 0 0
Italy
State/province [63] 0 0
Pisa
Country [64] 0 0
Italy
State/province [64] 0 0
Roma
Country [65] 0 0
Japan
State/province [65] 0 0
Aichi
Country [66] 0 0
Japan
State/province [66] 0 0
Chiba
Country [67] 0 0
Japan
State/province [67] 0 0
Fukuoka
Country [68] 0 0
Japan
State/province [68] 0 0
Hokkaido
Country [69] 0 0
Japan
State/province [69] 0 0
Ishikawa
Country [70] 0 0
Japan
State/province [70] 0 0
Kagawa
Country [71] 0 0
Japan
State/province [71] 0 0
Kanagawa
Country [72] 0 0
Japan
State/province [72] 0 0
Osaka
Country [73] 0 0
Japan
State/province [73] 0 0
Tokyo
Country [74] 0 0
Japan
State/province [74] 0 0
Hiroshima
Country [75] 0 0
Japan
State/province [75] 0 0
Saga
Country [76] 0 0
Japan
State/province [76] 0 0
Wakayama
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Kyonggi-do
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Seoul-teukbyeolsi [Seoul]
Country [79] 0 0
Korea, Republic of
State/province [79] 0 0
Seoul
Country [80] 0 0
Mexico
State/province [80] 0 0
Cdmx
Country [81] 0 0
Mexico
State/province [81] 0 0
Jalisco
Country [82] 0 0
Mexico
State/province [82] 0 0
Aguascalientes
Country [83] 0 0
Mexico
State/province [83] 0 0
Merida
Country [84] 0 0
Mexico
State/province [84] 0 0
Mexico City
Country [85] 0 0
Mexico
State/province [85] 0 0
Oaxaca
Country [86] 0 0
Mexico
State/province [86] 0 0
Puebla
Country [87] 0 0
New Zealand
State/province [87] 0 0
Auckland
Country [88] 0 0
New Zealand
State/province [88] 0 0
Christchurch
Country [89] 0 0
Poland
State/province [89] 0 0
Slaskie
Country [90] 0 0
Poland
State/province [90] 0 0
Zachodniopomorskie
Country [91] 0 0
Poland
State/province [91] 0 0
Myslowice
Country [92] 0 0
Poland
State/province [92] 0 0
Pila
Country [93] 0 0
Poland
State/province [93] 0 0
Warsaw
Country [94] 0 0
Poland
State/province [94] 0 0
Warszawa
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Moskva
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Sankt-Peterburg
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Krasnoyarsk
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Pyatigorsk
Country [99] 0 0
Spain
State/province [99] 0 0
Barcelona [Barcelona]
Country [100] 0 0
Spain
State/province [100] 0 0
Madrid
Country [101] 0 0
Spain
State/province [101] 0 0
Santiago de Compostela
Country [102] 0 0
Spain
State/province [102] 0 0
Sevilla
Country [103] 0 0
Spain
State/province [103] 0 0
Valencia
Country [104] 0 0
Taiwan
State/province [104] 0 0
Kaoshiung
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taichung
Country [106] 0 0
Taiwan
State/province [106] 0 0
Tainan
Country [107] 0 0
Taiwan
State/province [107] 0 0
Taipei
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taoyuan
Country [109] 0 0
Thailand
State/province [109] 0 0
Bangkok
Country [110] 0 0
Thailand
State/province [110] 0 0
Songkhla
Country [111] 0 0
Thailand
State/province [111] 0 0
Chiang Mai
Country [112] 0 0
Turkey
State/province [112] 0 0
Adana
Country [113] 0 0
Turkey
State/province [113] 0 0
Ankara
Country [114] 0 0
Turkey
State/province [114] 0 0
Antalya
Country [115] 0 0
Turkey
State/province [115] 0 0
Edirne
Country [116] 0 0
Turkey
State/province [116] 0 0
Erzurum
Country [117] 0 0
Turkey
State/province [117] 0 0
Istanbul
Country [118] 0 0
Turkey
State/province [118] 0 0
Konya
Country [119] 0 0
Turkey
State/province [119] 0 0
Malatya
Country [120] 0 0
United Kingdom
State/province [120] 0 0
London, City Of
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Birkenhead
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Glasgow
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Manchester
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eisai Inc.
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
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
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)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Llovet JM, Kudo M, Merle P, Meyer T, Qin S, Ikeda ... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03713593