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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
22/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
450
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
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Ohio
Country [16] 0 0
United States of America
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Oklahoma
Country [17] 0 0
United States of America
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Oregon
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United States of America
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Pennsylvania
Country [19] 0 0
United States of America
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Texas
Country [20] 0 0
United States of America
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West Virginia
Country [21] 0 0
Brazil
State/province [21] 0 0
Rio Grande Do Norte
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Brazil
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Rio Grande Do Sul
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Brazil
State/province [23] 0 0
Santa Catarina
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Brazil
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Sao Paulo
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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.


Results not provided in https://clinicaltrials.gov/study/NCT04246177