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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04246177




Registration number
NCT04246177
Ethics application status
Date submitted
27/01/2020
Date registered
29/01/2020

Titles & IDs
Public title
Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (MK-7902-012/E7080-G000-318/LEAP-012)
Scientific title
A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) With Pembrolizumab (MK-3475) in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepatocellular Carcinoma (LEAP-012)
Secondary ID [1] 0 0
MK-7902-012
Secondary ID [2] 0 0
7902-012
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 - Oral Placebo
Treatment: Drugs - IV Placebo
Treatment: Surgery - TACE

Experimental: Lenvatinib plus Pembrolizumab plus TACE - Participants will receive a combination of lenvatinib, pembrolizumab, and TACE. Lenvatinib will be administered at a dose of 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 during each 21-day cycle until progressive disease or unacceptable toxicity (up to 2 years \[\~35 cycles\] or longer with Sponsor approval). Pembrolizumab will be administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).

Active comparator: Oral Placebo plus IV Placebo plus TACE - Participants will receive a combination of lenvatinib-matching oral placebo, pembrolizumab-matching IV placebo, and TACE. Lenvatinib-matching oral placebo will be administered once a day during each 21-day cycle for up to 2 years (\~35 cycles) or longer with Sponsor approval and pembrolizumab-matching IV placebo will be administered once every 6 weeks (Q6W) for up to 2 years (\~17 doses). Participants will undergo TACE as a background procedure of chemotherapeutic and embolic agent(s).


Treatment: Drugs: Lenvatinib
Administered at a dose of 12 mg (for participants with screening body weight =60 kg) or 8 mg (for participants with screening body weight \<60 kg) via oral capsules once a day during each 21-day cycle.

Treatment: Other: Pembrolizumab
Administered via IV infusion at a dose of 400 mg once every 6 weeks (Q6W).

Treatment: Drugs: Oral Placebo
Lenvatinib-matching placebo administered via oral capsules once a day during each 21-day cycle.

Treatment: Drugs: IV Placebo
Pembrolizumab-matching placebo administered via IV infusion once every 6 weeks (Q6W).

Treatment: Surgery: TACE
Conducted as a background procedure of chemotherapeutic and embolic agent(s).

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Surgery
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 ~43 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~95 months
Secondary outcome [1] 0 0
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Timepoint [1] 0 0
Up to ~43 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) per mRECIST
Timepoint [2] 0 0
Up to ~95 months
Secondary outcome [3] 0 0
Disease Control Rate (DCR) per mRECIST
Timepoint [3] 0 0
Up to ~95 months
Secondary outcome [4] 0 0
Duration of Response (DOR) per mRECIST
Timepoint [4] 0 0
Up to ~95 months
Secondary outcome [5] 0 0
Time to Progression (TTP) per mRECIST
Timepoint [5] 0 0
Up to ~95 months
Secondary outcome [6] 0 0
Percentage of Participants Who Experience At Least One Adverse Event (AE)
Timepoint [6] 0 0
Up to ~95 months
Secondary outcome [7] 0 0
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE)
Timepoint [7] 0 0
Up to ~95 months
Secondary outcome [8] 0 0
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI)
Timepoint [8] 0 0
Up to ~95 months
Secondary outcome [9] 0 0
Percentage of Participants Who Discontinue Study Drug Due to an AE
Timepoint [9] 0 0
Up to ~95 months
Secondary outcome [10] 0 0
ORR per RESCIST 1.1
Timepoint [10] 0 0
Up to ~95 months
Secondary outcome [11] 0 0
DCR per RECIST 1.1
Timepoint [11] 0 0
Up to ~95 months
Secondary outcome [12] 0 0
DOR per RECIST 1.1
Timepoint [12] 0 0
Up to ~95 months
Secondary outcome [13] 0 0
TTP per RECIST 1.1
Timepoint [13] 0 0
Up to ~95 months

Eligibility
Key inclusion criteria
* Has a diagnosis of HCC confirmed by radiology, histology, or cytology
* Has HCC localized to the liver and not amenable to curative treatment
* Participants with Hepatitis C virus (HCV) are eligible if treatment was completed at least 1 month prior to starting study intervention
* Participants with Hepatitis B virus (HBV) are eligible
* Has adequately controlled blood pressure with or without antihypertensive medications
* Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Is currently a candidate for liver transplantation
* Has had gastric bleeding within the last 6 months
* Has ascites that is not controlled with medication
* Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as congestive heart failure
* Has a serious nonhealing wound, ulcer, or bone fracture
* Has received locoregional therapy to existing liver lesions

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 administering the treatment/s
The people assessing the outcomes
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
St George Hospital ( Site 0005) - Kogarah
Recruitment hospital [2] 0 0
Westmead Hospital-Gastroenterology & Hepatology ( Site 0009) - Westmead
Recruitment hospital [3] 0 0
Princess Alexandra Hospital ( Site 0006) - Brisbane
Recruitment hospital [4] 0 0
Austin Health ( Site 0008) - Heidelberg
Recruitment hospital [5] 0 0
Alfred Health ( Site 0004) - Melbourne
Recruitment hospital [6] 0 0
Royal Perth Hospital ( Site 0002) - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
6000 - Perth
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
Connecticut
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
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Mexico
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
West Virginia
Country [21] 0 0
Brazil
State/province [21] 0 0
Rio Grande Do Norte
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio Grande Do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Santa Catarina
Country [24] 0 0
Brazil
State/province [24] 0 0
Sao Paulo
Country [25] 0 0
Chile
State/province [25] 0 0
Araucania
Country [26] 0 0
Chile
State/province [26] 0 0
Region M. De Santiago
Country [27] 0 0
China
State/province [27] 0 0
Anhui
Country [28] 0 0
China
State/province [28] 0 0
Beijing
Country [29] 0 0
China
State/province [29] 0 0
Chongqing
Country [30] 0 0
China
State/province [30] 0 0
Fujian
Country [31] 0 0
China
State/province [31] 0 0
Guangdong
Country [32] 0 0
China
State/province [32] 0 0
Guangxi
Country [33] 0 0
China
State/province [33] 0 0
Hainan
Country [34] 0 0
China
State/province [34] 0 0
Heilongjiang
Country [35] 0 0
China
State/province [35] 0 0
Henan
Country [36] 0 0
China
State/province [36] 0 0
Hubei
Country [37] 0 0
China
State/province [37] 0 0
Hunan
Country [38] 0 0
China
State/province [38] 0 0
Jiangsu
Country [39] 0 0
China
State/province [39] 0 0
Jiangxi
Country [40] 0 0
China
State/province [40] 0 0
Shaanxi
Country [41] 0 0
China
State/province [41] 0 0
Shanghai
Country [42] 0 0
China
State/province [42] 0 0
Shanxi
Country [43] 0 0
China
State/province [43] 0 0
Sichuan
Country [44] 0 0
China
State/province [44] 0 0
Tianjin
Country [45] 0 0
China
State/province [45] 0 0
Yunnan
Country [46] 0 0
China
State/province [46] 0 0
Zhejiang
Country [47] 0 0
Colombia
State/province [47] 0 0
Antioquia
Country [48] 0 0
Colombia
State/province [48] 0 0
Distrito Capital De Bogota
Country [49] 0 0
Colombia
State/province [49] 0 0
Santander
Country [50] 0 0
Colombia
State/province [50] 0 0
Valle Del Cauca
Country [51] 0 0
Denmark
State/province [51] 0 0
Hovedstaden
Country [52] 0 0
Denmark
State/province [52] 0 0
Midtjylland
Country [53] 0 0
Denmark
State/province [53] 0 0
Syddanmark
Country [54] 0 0
France
State/province [54] 0 0
Auvergne
Country [55] 0 0
France
State/province [55] 0 0
Bouches-du-Rhone
Country [56] 0 0
France
State/province [56] 0 0
Gironde
Country [57] 0 0
France
State/province [57] 0 0
Meurthe-et-Moselle
Country [58] 0 0
France
State/province [58] 0 0
Val-de-Marne
Country [59] 0 0
Germany
State/province [59] 0 0
Baden-Wurttemberg
Country [60] 0 0
Germany
State/province [60] 0 0
Hessen
Country [61] 0 0
Germany
State/province [61] 0 0
Niedersachsen
Country [62] 0 0
Germany
State/province [62] 0 0
Nordrhein-Westfalen
Country [63] 0 0
Germany
State/province [63] 0 0
Sachsen-Anhalt
Country [64] 0 0
Germany
State/province [64] 0 0
Sachsen
Country [65] 0 0
Germany
State/province [65] 0 0
Schleswig-Holstein
Country [66] 0 0
Germany
State/province [66] 0 0
Berlin
Country [67] 0 0
Germany
State/province [67] 0 0
Hamburg
Country [68] 0 0
Hong Kong
State/province [68] 0 0
Shatin
Country [69] 0 0
Hungary
State/province [69] 0 0
Somogy
Country [70] 0 0
Hungary
State/province [70] 0 0
Zala
Country [71] 0 0
Hungary
State/province [71] 0 0
Budapest
Country [72] 0 0
Ireland
State/province [72] 0 0
Dublin
Country [73] 0 0
Israel
State/province [73] 0 0
Afula
Country [74] 0 0
Israel
State/province [74] 0 0
Haifa
Country [75] 0 0
Israel
State/province [75] 0 0
Jerusaelm
Country [76] 0 0
Israel
State/province [76] 0 0
Petah Tikva
Country [77] 0 0
Israel
State/province [77] 0 0
Tel Aviv
Country [78] 0 0
Italy
State/province [78] 0 0
Campania
Country [79] 0 0
Italy
State/province [79] 0 0
Milano
Country [80] 0 0
Italy
State/province [80] 0 0
Piemonte
Country [81] 0 0
Italy
State/province [81] 0 0
Sicilia
Country [82] 0 0
Italy
State/province [82] 0 0
Brescia
Country [83] 0 0
Italy
State/province [83] 0 0
Napoli
Country [84] 0 0
Italy
State/province [84] 0 0
Ravenna
Country [85] 0 0
Italy
State/province [85] 0 0
Roma
Country [86] 0 0
Japan
State/province [86] 0 0
Chiba
Country [87] 0 0
Japan
State/province [87] 0 0
Ehime
Country [88] 0 0
Japan
State/province [88] 0 0
Fukuoka
Country [89] 0 0
Japan
State/province [89] 0 0
Hokkaido
Country [90] 0 0
Japan
State/province [90] 0 0
Ishikawa
Country [91] 0 0
Japan
State/province [91] 0 0
Kagawa
Country [92] 0 0
Japan
State/province [92] 0 0
Kanagawa
Country [93] 0 0
Japan
State/province [93] 0 0
Nara
Country [94] 0 0
Japan
State/province [94] 0 0
Osaka
Country [95] 0 0
Japan
State/province [95] 0 0
Saitama
Country [96] 0 0
Japan
State/province [96] 0 0
Shizuoka
Country [97] 0 0
Japan
State/province [97] 0 0
Tochigi
Country [98] 0 0
Japan
State/province [98] 0 0
Hiroshima
Country [99] 0 0
Japan
State/province [99] 0 0
Kumamoto
Country [100] 0 0
Japan
State/province [100] 0 0
Kyoto
Country [101] 0 0
Japan
State/province [101] 0 0
Saga
Country [102] 0 0
Japan
State/province [102] 0 0
Tokyo
Country [103] 0 0
Korea, Republic of
State/province [103] 0 0
Jeonranamdo
Country [104] 0 0
Korea, Republic of
State/province [104] 0 0
Kyonggi-do
Country [105] 0 0
Korea, Republic of
State/province [105] 0 0
Pusan-Kwangyokshi
Country [106] 0 0
Korea, Republic of
State/province [106] 0 0
Taegu-Kwangyokshi
Country [107] 0 0
Korea, Republic of
State/province [107] 0 0
Seoul
Country [108] 0 0
Netherlands
State/province [108] 0 0
Limburg
Country [109] 0 0
Netherlands
State/province [109] 0 0
Noord-Holland
Country [110] 0 0
Netherlands
State/province [110] 0 0
Zuid-Holland
Country [111] 0 0
Netherlands
State/province [111] 0 0
Utrecht
Country [112] 0 0
New Zealand
State/province [112] 0 0
Auckland
Country [113] 0 0
Norway
State/province [113] 0 0
Oslo
Country [114] 0 0
Portugal
State/province [114] 0 0
Coimbra
Country [115] 0 0
Portugal
State/province [115] 0 0
Lisboa
Country [116] 0 0
Portugal
State/province [116] 0 0
Porto
Country [117] 0 0
Puerto Rico
State/province [117] 0 0
Ponce
Country [118] 0 0
Puerto Rico
State/province [118] 0 0
San Juan
Country [119] 0 0
Spain
State/province [119] 0 0
Madrid
Country [120] 0 0
Spain
State/province [120] 0 0
Valenciana, Comunitat
Country [121] 0 0
Spain
State/province [121] 0 0
Sevilla
Country [122] 0 0
Taiwan
State/province [122] 0 0
Kaohsiung
Country [123] 0 0
Taiwan
State/province [123] 0 0
Taichung
Country [124] 0 0
Taiwan
State/province [124] 0 0
Tainan
Country [125] 0 0
Taiwan
State/province [125] 0 0
Taipei
Country [126] 0 0
Taiwan
State/province [126] 0 0
Taoyuan
Country [127] 0 0
Thailand
State/province [127] 0 0
Krung Thep Maha Nakhon
Country [128] 0 0
Turkey
State/province [128] 0 0
Ankara
Country [129] 0 0
Turkey
State/province [129] 0 0
Edirne
Country [130] 0 0
Turkey
State/province [130] 0 0
Istanbul
Country [131] 0 0
Turkey
State/province [131] 0 0
Izmir
Country [132] 0 0
Turkey
State/province [132] 0 0
Konya
Country [133] 0 0
Turkey
State/province [133] 0 0
Malatya
Country [134] 0 0
Ukraine
State/province [134] 0 0
Kharkivska Oblast
Country [135] 0 0
Ukraine
State/province [135] 0 0
Kyivska Oblast
Country [136] 0 0
United Kingdom
State/province [136] 0 0
London, City Of

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.