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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03867084




Registration number
NCT03867084
Ethics application status
Date submitted
6/03/2019
Date registered
7/03/2019

Titles & IDs
Public title
Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)
Scientific title
A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma and Complete Radiological Response After Surgical Resection or Local Ablation (KEYNOTE-937)
Secondary ID [1] 0 0
MK-3475-937
Secondary ID [2] 0 0
3475-937
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 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: Other - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: Pembrolizumab - Participants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle for up to 17 cycles.

Placebo comparator: Placebo - Participants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.


Treatment: Other: Pembrolizumab
IV infusion of Pembrolizumab 200 mg.

Treatment: Drugs: Placebo
IV infusion of 0.9% normal saline.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recurrence-Free Survival (RFS)
Timepoint [1] 0 0
Up to ~6 years
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to ~8 years
Secondary outcome [1] 0 0
Percentage of Participants who Experience an Adverse Event (AE)
Timepoint [1] 0 0
Up to ~8 years
Secondary outcome [2] 0 0
Percentage of Participants who Discontinue Study Treatment Due to an AE
Timepoint [2] 0 0
Up to ~1 year
Secondary outcome [3] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score
Timepoint [3] 0 0
Baseline and time of last patient reported outcome (PRO) assessment (up to ~5 years)
Secondary outcome [4] 0 0
Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score
Timepoint [4] 0 0
Baseline and time of last PRO assessment (up to ~5 years)
Secondary outcome [5] 0 0
Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score
Timepoint [5] 0 0
Baseline and time of last PRO assessment (up to ~5 years)

Eligibility
Key inclusion criteria
* Has a diagnosis of HCC by radiological criteria and/or pathological confirmation.
* Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) confirming complete radiological response =4 weeks after complete surgical resection or local ablation. Randomization needs to occur within 12 weeks of the date of surgical resection or local ablation.
* Has no radiologic evidence of disease prior to enrollment.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day 1.
* Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
* Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
* Has controlled hepatitis B (Hep B).
* Has recovered adequately from toxicity and/or complications from the local intervention (surgical resection or local ablation) prior to starting study treatment.
* If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
* If undergoing surgical resection, has submitted a tumor tissue sample during Screening.
* 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
* Has a known additional malignancy that is progressing or has required active antineoplastic treatment (including hormonal) or surgery within the past 3 years.
* Has had esophageal or gastric variceal bleeding within the last 6 months.
* Has clinically apparent ascites on physical examination.
* Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
* Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has known active tuberculosis (TB; Bacillus tuberculosis).
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
* Has received prior systemic anti-cancer therapy for HCC including investigational agents.
* Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
* Has received a live vaccine within 30 days prior to the first dose of study treatment.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.
* Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* 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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/05/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2029
Actual
Sample size
Target
950
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital AW ( Site 0225) - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital ( Site 0226) - Liverpool
Recruitment hospital [3] 0 0
Princess Alexandra Hospital ( Site 0228) - Woollongabba
Recruitment hospital [4] 0 0
Royal Adelaide Hospital ( Site 0234) - Adelaide
Recruitment hospital [5] 0 0
Monash Health ( Site 0233) - Clayton
Recruitment hospital [6] 0 0
St Vincents Hospital Melbourne ( Site 0227) - Fitzroy
Recruitment hospital [7] 0 0
Alfred Health ( Site 0230) - Melbourne
Recruitment hospital [8] 0 0
Royal Perth Hospital ( Site 0229) - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4102 - Woollongabba
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 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
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United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
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Florida
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United States of America
State/province [5] 0 0
Indiana
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United States of America
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Iowa
Country [7] 0 0
United States of America
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Kentucky
Country [8] 0 0
United States of America
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Louisiana
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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New Mexico
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United States of America
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New York
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Ohio
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United States of America
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Oklahoma
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Washington
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Argentina
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Buenos Aires
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Argentina
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Caba
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Argentina
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Santa Fe
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Belgium
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Antwerpen
Country [22] 0 0
Belgium
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Bruxelles-Capitale, Region De
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Belgium
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Oost-Vlaanderen
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Belgium
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Vlaams-Brabant
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Brazil
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Parana
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Brazil
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Pernambuco
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Brazil
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Rio Grande Do Sul
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Brazil
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Santa Catarina
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Brazil
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Sao Paulo
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Brazil
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Rio de Janeiro
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Bulgaria
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Plovdiv
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Canada
State/province [32] 0 0
Nova Scotia
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Canada
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Quebec
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China
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Anhui
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China
State/province [35] 0 0
Beijing
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China
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Fujian
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China
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Guangdong
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China
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Hubei
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China
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Hunan
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China
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Shanghai
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China
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Shanxi
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China
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Sichuan
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China
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Xinjiang
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China
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Zhejiang
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Denmark
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Hovedstaden
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Denmark
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Midtjylland
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Denmark
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Syddanmark
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France
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Bas-Rhin
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France
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Bouches-du-Rhone
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Gironde
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Haute-Garonne
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Hauts-de-Seine
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Herault
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France
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Nord
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France
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Val-de-Marne
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
Country [60] 0 0
Germany
State/province [60] 0 0
Nordrhein-Westfalen
Country [61] 0 0
Germany
State/province [61] 0 0
Sachsen
Country [62] 0 0
Germany
State/province [62] 0 0
Berlin
Country [63] 0 0
Germany
State/province [63] 0 0
Hamburg
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Hong Kong
State/province [64] 0 0
Hong Kong
Country [65] 0 0
Hong Kong
State/province [65] 0 0
Tuen Mun
Country [66] 0 0
Hungary
State/province [66] 0 0
Bacs-Kiskun
Country [67] 0 0
Hungary
State/province [67] 0 0
Csongrad
Country [68] 0 0
Hungary
State/province [68] 0 0
Somogy
Country [69] 0 0
Hungary
State/province [69] 0 0
Budapest
Country [70] 0 0
Hungary
State/province [70] 0 0
Debrecen
Country [71] 0 0
Ireland
State/province [71] 0 0
Dublin
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Israel
State/province [72] 0 0
Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
Country [76] 0 0
Israel
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Tel Aviv
Country [77] 0 0
Italy
State/province [77] 0 0
Abruzzo
Country [78] 0 0
Italy
State/province [78] 0 0
Piemonte
Country [79] 0 0
Italy
State/province [79] 0 0
Sicilia
Country [80] 0 0
Italy
State/province [80] 0 0
Bari
Country [81] 0 0
Italy
State/province [81] 0 0
Bologna
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Italy
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Firenze
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Italy
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Milano
Country [84] 0 0
Italy
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Napoli
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Italy
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Pisa
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Japan
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Ehime
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Japan
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Fukuoka
Country [88] 0 0
Japan
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Hokkaido
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Japan
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Ishikawa
Country [90] 0 0
Japan
State/province [90] 0 0
Kagawa
Country [91] 0 0
Japan
State/province [91] 0 0
Kanagawa
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Japan
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Osaka
Country [93] 0 0
Japan
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Saitama
Country [94] 0 0
Japan
State/province [94] 0 0
Tokyo
Country [95] 0 0
Japan
State/province [95] 0 0
Chiba
Country [96] 0 0
Japan
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Hiroshima
Country [97] 0 0
Japan
State/province [97] 0 0
Kyoto
Country [98] 0 0
Japan
State/province [98] 0 0
Saga
Country [99] 0 0
Japan
State/province [99] 0 0
Wakayama
Country [100] 0 0
Korea, Republic of
State/province [100] 0 0
Kyonggi-do
Country [101] 0 0
Korea, Republic of
State/province [101] 0 0
Seoul
Country [102] 0 0
Malaysia
State/province [102] 0 0
Kelantan
Country [103] 0 0
Malaysia
State/province [103] 0 0
Pulau Pinang
Country [104] 0 0
Malaysia
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Sarawak
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Malaysia
State/province [105] 0 0
Wilayah Persekutuan Putrajaya
Country [106] 0 0
Malaysia
State/province [106] 0 0
Kuala Lumpur
Country [107] 0 0
New Zealand
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Canterbury
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New Zealand
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Auckland
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Norway
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Oslo
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Poland
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Dolnoslaskie
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Poland
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Lubelskie
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Poland
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Mazowieckie
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Poland
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Pomorskie
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Poland
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Slaskie
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Poland
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Warminsko-mazurskie
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Poland
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Zachodniopomorskie
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Russian Federation
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Altayskiy Kray
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Russian Federation
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Krasnoyarskiy Kray
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Moskva
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Nizhegorodskaya Oblast
Country [121] 0 0
Russian Federation
State/province [121] 0 0
Samarskaya Oblast
Country [122] 0 0
Russian Federation
State/province [122] 0 0
Sankt-Peterburg
Country [123] 0 0
Russian Federation
State/province [123] 0 0
Tomskaya Oblast
Country [124] 0 0
Spain
State/province [124] 0 0
Asturias
Country [125] 0 0
Spain
State/province [125] 0 0
Barcelona
Country [126] 0 0
Spain
State/province [126] 0 0
Gipuzkoa
Country [127] 0 0
Spain
State/province [127] 0 0
La Coruna
Country [128] 0 0
Spain
State/province [128] 0 0
Madrid
Country [129] 0 0
Spain
State/province [129] 0 0
Sevilla
Country [130] 0 0
Spain
State/province [130] 0 0
Zaragoza
Country [131] 0 0
Sweden
State/province [131] 0 0
Skane Lan
Country [132] 0 0
Sweden
State/province [132] 0 0
Stockholms Lan
Country [133] 0 0
Sweden
State/province [133] 0 0
Vasterbottens Lan
Country [134] 0 0
Sweden
State/province [134] 0 0
Vastra Gotalands Lan
Country [135] 0 0
Switzerland
State/province [135] 0 0
Aargau
Country [136] 0 0
Switzerland
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Basel-Stadt
Country [137] 0 0
Switzerland
State/province [137] 0 0
Sankt Gallen
Country [138] 0 0
Switzerland
State/province [138] 0 0
Vaud
Country [139] 0 0
Switzerland
State/province [139] 0 0
Zurich
Country [140] 0 0
Switzerland
State/province [140] 0 0
Geneve
Country [141] 0 0
Taiwan
State/province [141] 0 0
Kaohsiung
Country [142] 0 0
Taiwan
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Taichung
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Taiwan
State/province [143] 0 0
Tainan
Country [144] 0 0
Taiwan
State/province [144] 0 0
Taipei
Country [145] 0 0
Taiwan
State/province [145] 0 0
Taoyuan
Country [146] 0 0
Thailand
State/province [146] 0 0
Krung Thep Maha Nakhon
Country [147] 0 0
Thailand
State/province [147] 0 0
Chiang Mai
Country [148] 0 0
Thailand
State/province [148] 0 0
Khon Kaen
Country [149] 0 0
Turkey
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Tekirdas
Country [150] 0 0
Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Aydin
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Turkey
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Istanbul
Country [154] 0 0
Turkey
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Izmir
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Turkey
State/province [155] 0 0
Konya
Country [156] 0 0
Turkey
State/province [156] 0 0
Malatya
Country [157] 0 0
Turkey
State/province [157] 0 0
Mersin
Country [158] 0 0
Ukraine
State/province [158] 0 0
Chernivetska Oblast
Country [159] 0 0
Ukraine
State/province [159] 0 0
Kharkivska Oblast
Country [160] 0 0
Ukraine
State/province [160] 0 0
Kyivska Oblast
Country [161] 0 0
Ukraine
State/province [161] 0 0
Odeska Oblast
Country [162] 0 0
Ukraine
State/province [162] 0 0
Zaporizka Oblast
Country [163] 0 0
Ukraine
State/province [163] 0 0
Kyiv
Country [164] 0 0
United Kingdom
State/province [164] 0 0
Cambridgeshire
Country [165] 0 0
United Kingdom
State/province [165] 0 0
Derbyshire
Country [166] 0 0
United Kingdom
State/province [166] 0 0
Glasgow City
Country [167] 0 0
United Kingdom
State/province [167] 0 0
London, City Of
Country [168] 0 0
United Kingdom
State/province [168] 0 0
Northern Ireland
Country [169] 0 0
United Kingdom
State/province [169] 0 0
Wirral
Country [170] 0 0
United Kingdom
State/province [170] 0 0
Coventry
Country [171] 0 0
United Kingdom
State/province [171] 0 0
Leeds
Country [172] 0 0
United Kingdom
State/province [172] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

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/NCT03867084