Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03833167




Registration number
NCT03833167
Ethics application status
Date submitted
4/02/2019
Date registered
6/02/2019
Date last updated
12/11/2024

Titles & IDs
Public title
Pembrolizumab (MK-3475) Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Pembrolizumab Versus Placebo as Adjuvant Therapy Following Surgery and Radiation in Participants With High-risk Locally Advanced Cutaneous Squamous Cell Carcinoma (LA cSCC) (KEYNOTE-630)
Secondary ID [1] 0 0
MK-3475-630
Secondary ID [2] 0 0
3475-630
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab 400 mg
Treatment: Drugs - Placebo

Experimental: Pembrolizumab - Participants receive 400 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants that complete 9 cycles of pembrolizumab and experience biopsy-proven-disease recurrence may be eligible to receive up to 18 additional cycles of pembrolizumab in an open-label design.

Placebo comparator: Placebo - Participants receive placebo by IV infusion administered on Day 1 of each 42-day cycle (Q6W) for up to 9 cycles. Participants treated with placebo who experience biopsy-proven-disease recurrence may be eligible to receive up to 18 cycles of pembrolizumab in an open-label design.


Treatment: Other: Pembrolizumab 400 mg
Administered by IV infusion on Day 1 of each 42-day cycle

Treatment: Drugs: Placebo
Administered by IV infusion on Day 1 of each 42-day cycle
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) as Assessed by the Investigator and Confirmed by Biopsy
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 60 months
Secondary outcome [2] 0 0
Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
Timepoint [2] 0 0
Baseline and up to approximately 60 months
Secondary outcome [3] 0 0
Change From Baseline in Physical Functioning Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 1-5 Score
Timepoint [3] 0 0
Baseline and up to approximately 60 months
Secondary outcome [4] 0 0
Percentage of Participants Who Experience an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 63 months
Secondary outcome [5] 0 0
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [5] 0 0
Up to approximately 38 months

Eligibility
Key inclusion criteria
* Has histologically confirmed cutaneous squamous cell carcinoma (cSCC) as the primary site of malignancy (metastatic skin involvement from another type of primary cancer or from an unknown primary cancer is not permitted)
* Has histologically confirmed LA cSCC with =1 high-risk feature(s) as the primary site of malignancy
* Has undergone complete macroscopic resection of all known cSCC disease with or without microscopic positive margins. For those participants with residual microscopic positive margin involvement, confirmation that additional re-excision is not possible must be provided
* Has completed adjuvant radiotherapy (RT) for LA cSCC with last dose of RT =4 weeks and =16 weeks from randomization
* Has received an adequate post-op dose of RT (either hypofractionated or conventional)
* Is disease free as assessed by the investigator with complete radiographic staging assessment =28 days from randomization
* Is not pregnant or breastfeeding
* Is not a person of childbearing potential (POCBP)
* Has a negative pregnancy test =72 hours before the first dose of study intervention.
* Has provided an archival or newly-obtained tumor tissue sample adequate for Programmed Cell Death Ligand 1 (PD-L1) testing as determined by central laboratory testing
* Has a life expectancy of >3 months
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 =10 days prior to the first dose of study intervention.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has macroscopic residual cSCC after surgery and/or recurrence with active cSCC disease before randomization
* Has any other histologic type of skin cancer other than invasive cSCC (eg, basal cell carcinoma) that has not been definitively treated with surgery or radiation; Bowen's disease; Merkel cell carcinoma; or melanoma
* Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-PD-L1, or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another costimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
* Has received prior systemic anticancer therapy including investigational agents for cSCC =4 weeks prior to before start of study intervention.
* Has not recovered from all radiation-related toxicities and has not had radiation pneumonitis
* Has received a live vaccine =30 days prior to the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
* Has known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Other exceptions may be considered with Sponsor consultation. Note: Participants with low risk early-stage prostate cancer defined as below are not excluded: Stage T1c or T2a with a Gleason score =6 and a prostate-specific antigen (=10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study allocation. Early stage asymptomatic CLL without prior treatment and without any of the risk features (unmutated IGHV, lymphocytes >15,000µL, palpable lymph nodes) will be eligible for the study
* Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
* 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 a known history of human immunodeficiency virus (HIV) infection
* Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected) infection
* 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 allogeneic 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
1/04/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/09/2028
Actual
Sample size
Target
Accrual to date
Final
450
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse ( Site 0051) - Camperdown
Recruitment hospital [2] 0 0
Lismore Base Hospital ( Site 0050) - Lismore
Recruitment hospital [3] 0 0
Orange Health Services ( Site 0053) - Orange
Recruitment hospital [4] 0 0
Royal North Shore Hospital ( Site 0052) - St Leonards
Recruitment hospital [5] 0 0
Gold Coast University Hospital ( Site 0054) - Southport
Recruitment hospital [6] 0 0
Sunshine Coast University Private Hospital-Coastal Cancer Care ( Site 0056) - Sunshine Coast
Recruitment hospital [7] 0 0
Alfred Health ( Site 0055) - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2480 - Lismore
Recruitment postcode(s) [3] 0 0
2800 - Orange
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
4575 - Sunshine Coast
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
West Virginia
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Argentina
State/province [23] 0 0
Cordoba
Country [24] 0 0
Argentina
State/province [24] 0 0
Santa Fe
Country [25] 0 0
Argentina
State/province [25] 0 0
Caba
Country [26] 0 0
Argentina
State/province [26] 0 0
La Rioja
Country [27] 0 0
Argentina
State/province [27] 0 0
Santiago del Estero
Country [28] 0 0
Brazil
State/province [28] 0 0
Ceara
Country [29] 0 0
Brazil
State/province [29] 0 0
Parana
Country [30] 0 0
Brazil
State/province [30] 0 0
Rio Grande Do Sul
Country [31] 0 0
Brazil
State/province [31] 0 0
Rio de Janeiro
Country [32] 0 0
Brazil
State/province [32] 0 0
Sao Paulo
Country [33] 0 0
Canada
State/province [33] 0 0
Alberta
Country [34] 0 0
Canada
State/province [34] 0 0
Ontario
Country [35] 0 0
Canada
State/province [35] 0 0
Quebec
Country [36] 0 0
Chile
State/province [36] 0 0
Araucania
Country [37] 0 0
Chile
State/province [37] 0 0
Region M. De Santiago
Country [38] 0 0
Chile
State/province [38] 0 0
Antofagasta
Country [39] 0 0
Colombia
State/province [39] 0 0
Cordoba
Country [40] 0 0
Colombia
State/province [40] 0 0
Distrito Capital De Bogota
Country [41] 0 0
Colombia
State/province [41] 0 0
Risaralda
Country [42] 0 0
Colombia
State/province [42] 0 0
Santander
Country [43] 0 0
Colombia
State/province [43] 0 0
Valle Del Cauca
Country [44] 0 0
France
State/province [44] 0 0
Alpes-Maritimes
Country [45] 0 0
France
State/province [45] 0 0
Bouches-du-Rhone
Country [46] 0 0
France
State/province [46] 0 0
Calvados
Country [47] 0 0
France
State/province [47] 0 0
Doubs
Country [48] 0 0
France
State/province [48] 0 0
Drome
Country [49] 0 0
France
State/province [49] 0 0
Gard
Country [50] 0 0
France
State/province [50] 0 0
Gironde
Country [51] 0 0
France
State/province [51] 0 0
Haute-Garonne
Country [52] 0 0
France
State/province [52] 0 0
Haute-Savoie
Country [53] 0 0
France
State/province [53] 0 0
Herault
Country [54] 0 0
France
State/province [54] 0 0
Nord
Country [55] 0 0
France
State/province [55] 0 0
Puy-de-Dome
Country [56] 0 0
France
State/province [56] 0 0
Rhone
Country [57] 0 0
France
State/province [57] 0 0
Seine-Saint-Denis
Country [58] 0 0
France
State/province [58] 0 0
Val-de-Marne
Country [59] 0 0
France
State/province [59] 0 0
Vienne
Country [60] 0 0
Germany
State/province [60] 0 0
Baden-Wurttemberg
Country [61] 0 0
Germany
State/province [61] 0 0
Bayern
Country [62] 0 0
Germany
State/province [62] 0 0
Hessen
Country [63] 0 0
Germany
State/province [63] 0 0
Niedersachsen
Country [64] 0 0
Germany
State/province [64] 0 0
Nordrhein-Westfalen
Country [65] 0 0
Germany
State/province [65] 0 0
Berlin
Country [66] 0 0
Germany
State/province [66] 0 0
Hamburg
Country [67] 0 0
Greece
State/province [67] 0 0
Achaia
Country [68] 0 0
Greece
State/province [68] 0 0
Attiki
Country [69] 0 0
Greece
State/province [69] 0 0
Thessaloniki
Country [70] 0 0
Hungary
State/province [70] 0 0
Baranya
Country [71] 0 0
Hungary
State/province [71] 0 0
Csongrad
Country [72] 0 0
Hungary
State/province [72] 0 0
Szabolcs-Szatmar-Bereg
Country [73] 0 0
Hungary
State/province [73] 0 0
Vas
Country [74] 0 0
Hungary
State/province [74] 0 0
Budapest
Country [75] 0 0
Ireland
State/province [75] 0 0
Dublin
Country [76] 0 0
Israel
State/province [76] 0 0
Beer Sheva
Country [77] 0 0
Israel
State/province [77] 0 0
Haifa
Country [78] 0 0
Israel
State/province [78] 0 0
Jerusalem
Country [79] 0 0
Israel
State/province [79] 0 0
Kfar-Saba
Country [80] 0 0
Israel
State/province [80] 0 0
Petah Tiqwa
Country [81] 0 0
Israel
State/province [81] 0 0
Ramat Gan
Country [82] 0 0
Israel
State/province [82] 0 0
Tel-Aviv
Country [83] 0 0
Italy
State/province [83] 0 0
Puglia
Country [84] 0 0
Italy
State/province [84] 0 0
Toscana
Country [85] 0 0
Italy
State/province [85] 0 0
Milano
Country [86] 0 0
Italy
State/province [86] 0 0
Napoli
Country [87] 0 0
Mexico
State/province [87] 0 0
Chiapas
Country [88] 0 0
Mexico
State/province [88] 0 0
Coahuila
Country [89] 0 0
Mexico
State/province [89] 0 0
Jalisco
Country [90] 0 0
Mexico
State/province [90] 0 0
Yucatan
Country [91] 0 0
Mexico
State/province [91] 0 0
Chihuahua
Country [92] 0 0
Mexico
State/province [92] 0 0
Veracruz
Country [93] 0 0
New Zealand
State/province [93] 0 0
Auckland
Country [94] 0 0
Norway
State/province [94] 0 0
Hordaland
Country [95] 0 0
Norway
State/province [95] 0 0
Sor-Trondelag
Country [96] 0 0
Norway
State/province [96] 0 0
Oslo
Country [97] 0 0
Poland
State/province [97] 0 0
Malopolskie
Country [98] 0 0
Poland
State/province [98] 0 0
Mazowieckie
Country [99] 0 0
Poland
State/province [99] 0 0
Pomorskie
Country [100] 0 0
Poland
State/province [100] 0 0
Slaskie
Country [101] 0 0
Portugal
State/province [101] 0 0
Faro
Country [102] 0 0
Portugal
State/province [102] 0 0
Lisboa
Country [103] 0 0
Portugal
State/province [103] 0 0
Porto
Country [104] 0 0
Romania
State/province [104] 0 0
Bihor
Country [105] 0 0
Romania
State/province [105] 0 0
Bucuresti
Country [106] 0 0
Romania
State/province [106] 0 0
Cluj
Country [107] 0 0
Romania
State/province [107] 0 0
Dolj
Country [108] 0 0
Romania
State/province [108] 0 0
Timis
Country [109] 0 0
Russian Federation
State/province [109] 0 0
Altayskiy Kray
Country [110] 0 0
Russian Federation
State/province [110] 0 0
Baskortostan, Respublika
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Kaluzskaja Oblast
Country [112] 0 0
Russian Federation
State/province [112] 0 0
Krasnodarskiy Kray
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Moskovskaya Oblast
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Moskva
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Nizhegorodskaya Oblast
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Sankt-Peterburg
Country [117] 0 0
Russian Federation
State/province [117] 0 0
Udmurtskaya Respublika
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Yaroslavskaya Oblast
Country [119] 0 0
Spain
State/province [119] 0 0
Barcelona
Country [120] 0 0
Spain
State/province [120] 0 0
Cantabria
Country [121] 0 0
Spain
State/province [121] 0 0
Cataluna
Country [122] 0 0
Spain
State/province [122] 0 0
Gipuzkoa
Country [123] 0 0
Spain
State/province [123] 0 0
Madrid
Country [124] 0 0
Spain
State/province [124] 0 0
Malaga
Country [125] 0 0
Ukraine
State/province [125] 0 0
Ivano-Frankivska Oblast
Country [126] 0 0
Ukraine
State/province [126] 0 0
Kharkivska Oblast
Country [127] 0 0
Ukraine
State/province [127] 0 0
Kirovohradska Oblast
Country [128] 0 0
Ukraine
State/province [128] 0 0
Sumska Oblast
Country [129] 0 0
Ukraine
State/province [129] 0 0
Kyiv
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Cornwall
Country [131] 0 0
United Kingdom
State/province [131] 0 0
London, City Of
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Oxfordshire

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, study that compares pembrolizumab (MK-3475) with placebo given as adjuvant therapy in participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) that have undergone surgery with curative intent in combination with radiotherapy. The primary hypothesis is that pembrolizumab is superior to placebo in increasing recurrence free survival (RFS).
Trial website
https://clinicaltrials.gov/study/NCT03833167
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03833167