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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04246177
Ethics application status
Date submitted
27/01/2020
Date registered
29/01/2020
Date last updated
26/11/2020

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
2019-002345-37
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
Other interventions - 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.

Other interventions: 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
Other interventions
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) - PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR).
Timepoint [1] 0 0
Up to ~5 years
Primary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to death due to any cause.
Timepoint [2] 0 0
Up to ~5 years
Secondary outcome [1] 0 0
PFS per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) - PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.
Timepoint [1] 0 0
Up to ~5 years
Secondary outcome [2] 0 0
Objective Response Rate (ORR) per mRECIST - ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions). Responses are according to mRECIST as assessed by BICR.
Timepoint [2] 0 0
Up to ~5 years
Secondary outcome [3] 0 0
Disease Control Rate (DCR) per mRECIST - DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of any intratumoral arterial enhancement in all target lesions), PR (at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions), or stable disease (SD). Responses are according to mRECIST as assessed by BICR.
Timepoint [3] 0 0
Up to ~5 years
Secondary outcome [4] 0 0
Duration of Response (DOR) per mRECIST - DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of any intratumoral arterial enhancement in all target lesions) or PR (at least a 30% decrease in the sum of diameters of viable [enhancement in the arterial phase] target lesions, taking as reference the baseline sum of the diameters of target lesions) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to mRECIST as assessed by BICR.
Timepoint [4] 0 0
Up to ~5 years
Secondary outcome [5] 0 0
Time to Progression (TTP) per mRECIST - TTP is defined as the time from randomization to the first documented disease progression. Responses are according to mRECIST as assessed by BICR.
Timepoint [5] 0 0
Up to ~5 years
Secondary outcome [6] 0 0
Percentage of Participants Who Experience At Least One Adverse Event (AE) - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
Timepoint [6] 0 0
Up to ~5 years
Secondary outcome [7] 0 0
Percentage of Participants Who Experience At Least One Serious Adverse Event (SAE) - An SAE is an AE that results in death, is life threatening, requires or prolongs a hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants who experience at least one SAE will be reported.
Timepoint [7] 0 0
Up to ~5 years
Secondary outcome [8] 0 0
Percentage of Participants Who Experience At Least One Hepatic Event of Clinical Interest (ECI) - Percentage of participants with Hepatic ECIs not due to disease progression or TACE as assessed by the investigator will be reported.
Timepoint [8] 0 0
Up to ~5 years
Secondary outcome [9] 0 0
Percentage of Participants Who Discontinue Study Drug Due to an AE - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study drug due to an AE will be reported.
Timepoint [9] 0 0
Up to ~5 years
Secondary outcome [10] 0 0
ORR per RESCIST 1.1 - ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by BICR.
Timepoint [10] 0 0
Up to ~5 years
Secondary outcome [11] 0 0
DCR per RECIST 1.1 - DCR is defined as the percentage of participants who have a best overall response of CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), or SD. Responses are according to RECIST 1.1 as assessed by BICR.
Timepoint [11] 0 0
Up to ~5 years
Secondary outcome [12] 0 0
DOR per RECIST 1.1 - DOR is determined by disease assessment and is defined as the time from the first documented evidence of a response of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) until the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR.
Timepoint [12] 0 0
Up to ~5 years
Secondary outcome [13] 0 0
TTP per RECIST 1.1 - TTP is defined as the time from randomization to the first documented disease progression. Responses are according to RECIST 1.1 as assessed by BICR.
Timepoint [13] 0 0
Up to ~5 years

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 as long as their virus is well
controlled

- Has adequately controlled blood pressure with or without antihypertensive medications

- Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Gender
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

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
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
Princess Alexandra Hospital ( Site 0006) - Brisbane
Recruitment hospital [3] 0 0
Austin Health ( Site 0008) - Heidelberg
Recruitment hospital [4] 0 0
Alfred Health ( Site 0004) - Melbourne
Recruitment hospital [5] 0 0
Royal Perth Hospital ( Site 0002) - Perth
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Idaho
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
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
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
Brazil
State/province [15] 0 0
Santa Catarina
Country [16] 0 0
Brazil
State/province [16] 0 0
Sao Paulo
Country [17] 0 0
Chile
State/province [17] 0 0
Araucania
Country [18] 0 0
Chile
State/province [18] 0 0
Region M. De Santiago
Country [19] 0 0
China
State/province [19] 0 0
Anhui
Country [20] 0 0
China
State/province [20] 0 0
Beijing
Country [21] 0 0
China
State/province [21] 0 0
Guangdong
Country [22] 0 0
China
State/province [22] 0 0
Hainan
Country [23] 0 0
China
State/province [23] 0 0
Henan
Country [24] 0 0
China
State/province [24] 0 0
Hubei
Country [25] 0 0
China
State/province [25] 0 0
Hunan
Country [26] 0 0
China
State/province [26] 0 0
Shanxi
Country [27] 0 0
China
State/province [27] 0 0
Tianjin
Country [28] 0 0
China
State/province [28] 0 0
Zhejiang
Country [29] 0 0
Colombia
State/province [29] 0 0
Distrito Capital De Bogota
Country [30] 0 0
Colombia
State/province [30] 0 0
Santander
Country [31] 0 0
Colombia
State/province [31] 0 0
Valle Del Cauca
Country [32] 0 0
Denmark
State/province [32] 0 0
Hovedstaden
Country [33] 0 0
Denmark
State/province [33] 0 0
Syddanmark
Country [34] 0 0
France
State/province [34] 0 0
Auvergne
Country [35] 0 0
France
State/province [35] 0 0
Bouches-du-Rhone
Country [36] 0 0
France
State/province [36] 0 0
Meurthe-et-Moselle
Country [37] 0 0
France
State/province [37] 0 0
Val-de-Marne
Country [38] 0 0
Israel
State/province [38] 0 0
Yerushalayim
Country [39] 0 0
Israel
State/province [39] 0 0
Haifa
Country [40] 0 0
Israel
State/province [40] 0 0
Petah Tikva
Country [41] 0 0
Israel
State/province [41] 0 0
Tel Aviv
Country [42] 0 0
Italy
State/province [42] 0 0
Roma
Country [43] 0 0
Japan
State/province [43] 0 0
Chiba
Country [44] 0 0
Japan
State/province [44] 0 0
Ehime
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hokkaido
Country [47] 0 0
Japan
State/province [47] 0 0
Ishikawa
Country [48] 0 0
Japan
State/province [48] 0 0
Kagawa
Country [49] 0 0
Japan
State/province [49] 0 0
Kanagawa
Country [50] 0 0
Japan
State/province [50] 0 0
Nara
Country [51] 0 0
Japan
State/province [51] 0 0
Osaka
Country [52] 0 0
Japan
State/province [52] 0 0
Shizuoka
Country [53] 0 0
Japan
State/province [53] 0 0
Tochigi
Country [54] 0 0
Japan
State/province [54] 0 0
Hiroshima
Country [55] 0 0
Japan
State/province [55] 0 0
Kyoto
Country [56] 0 0
Japan
State/province [56] 0 0
Saga
Country [57] 0 0
Japan
State/province [57] 0 0
Tokyo
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Jeonranamdo
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Kyonggi-do
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Taegu-Kwangyokshi
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Seoul
Country [62] 0 0
Netherlands
State/province [62] 0 0
Limburg
Country [63] 0 0
Netherlands
State/province [63] 0 0
Zuid-Holland
Country [64] 0 0
New Zealand
State/province [64] 0 0
Auckland
Country [65] 0 0
Portugal
State/province [65] 0 0
Porto
Country [66] 0 0
Puerto Rico
State/province [66] 0 0
Ponce
Country [67] 0 0
Puerto Rico
State/province [67] 0 0
San Juan
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Taiwan
State/province [69] 0 0
Changhua
Country [70] 0 0
Taiwan
State/province [70] 0 0
Kaohsiung
Country [71] 0 0
Taiwan
State/province [71] 0 0
Taipei
Country [72] 0 0
Taiwan
State/province [72] 0 0
Taoyuan
Country [73] 0 0
Thailand
State/province [73] 0 0
Krung Thep Maha Nakhon
Country [74] 0 0
Turkey
State/province [74] 0 0
Ankara
Country [75] 0 0
Turkey
State/province [75] 0 0
Edirne
Country [76] 0 0
Turkey
State/province [76] 0 0
Izmir
Country [77] 0 0
Turkey
State/province [77] 0 0
Konya
Country [78] 0 0
Turkey
State/province [78] 0 0
Malatya
Country [79] 0 0
Ukraine
State/province [79] 0 0
Kharkivska Oblast
Country [80] 0 0
Ukraine
State/province [80] 0 0
Kyivska Oblast

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
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
The purpose of this study is to evaluate the efficacy and safety of lenvatinib and
pembrolizumab in combination with TACE versus TACE plus oral and intravenous (IV) placebos in
participants with incurable, non-metastatic hepatocellular carcinoma (HCC). The primary
hypotheses are that pembrolizumab plus lenvatinib in combination with TACE is superior to
placebo plus TACE with respect to progression-free survival (PFS) and overall survival (OS).
Trial website
https://clinicaltrials.gov/show/NCT04246177
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04246177