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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03924869




Registration number
NCT03924869
Ethics application status
Date submitted
22/04/2019
Date registered
23/04/2019

Titles & IDs
Public title
Efficacy and Safety Study of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Adults With Unresected Stage I or II Non-Small Cell Lung Cancer (NSCLC) (MK-3475-867/KEYNOTE-867)
Scientific title
A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Participants With Unresected Stages I or II Non Small Cell Lung Cancer (NSCLC) (KEYNOTE-867)
Secondary ID [1] 0 0
MK-3475-867
Secondary ID [2] 0 0
3475-867
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Stereotactic Body Radiotherapy (SBRT)
Treatment: Other - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: SBRT+Pembolizumab - Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray \[Gy\] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.

Placebo comparator: SBRT+Placebo - Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.


Treatment: Other: Stereotactic Body Radiotherapy (SBRT)
SBRT

Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Placebo
IV infusion
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
Event-free Survival (EFS)
Timepoint [1] 0 0
Up to approximately 68 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 81 months
Secondary outcome [2] 0 0
Time to Death or Distant Metastases (TDDM)
Timepoint [2] 0 0
Up to approximately 81 months
Secondary outcome [3] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 16 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 1 year
Secondary outcome [5] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score
Timepoint [5] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [6] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Cough (Item 31) Score
Timepoint [6] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [7] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Chest Pain (Item 10) Score
Timepoint [7] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [8] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score
Timepoint [8] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [9] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score
Timepoint [9] 0 0
Baseline and up to approximately 52 weeks

Eligibility
Key inclusion criteria
* Has previously untreated non-small cell lung cancer (NSCLC) diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) NSCLC (American Joint Committee on Cancer, AJCC) by chest computed tomography (CT) and positron emission tomography (PET) scan. Participants with pericardium invasion, >2 nodules or 2 nodules that cannot be treated in one field (>2 cm apart and/or total planned target volume [PTV] >163 cc) and diaphragm elevation suggestive of phrenic nerve invasion are excluded
* Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the site's multi-disciplinary tumor board. Medically operable participants who decide to treat with stereotactic body radiotherapy (SBRT) as definitive therapy rather than surgery are also eligible, if patient's unwillingness to undergo surgical resection is clearly documented
* Has a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
* Is able to receive SBRT and does not have an ultra-centrally located tumor
* Has adequate organ function within 7 days prior to the start of study treatment
* A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) not a women of childbearing potential (WOCBP) OR b) A WOCBP and uses contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
* Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per study protocol, unless confirmed to be azoospermic
* Has a radiation therapy plan approved by the central radiation therapy quality assurance vendor
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137])
* Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast
* Has received a live vaccine within 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 intervention administration
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast c carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has a known hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has an active autoimmune disease that has required systemic treatment in past 2 years, except replacement therapy
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
* 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 pembrolizumab/placebo and 180 days after the last radiotherapy dose
* Have not adequately recovered from major surgery or have ongoing surgical complications
* 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
25/06/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
436
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Port Macquarie Base Hospital ( Site 2500) - Port Macquarie
Recruitment hospital [2] 0 0
GenesisCare North Shore ( Site 2508) - St Leonards
Recruitment hospital [3] 0 0
Royal Brisbane and Women s Hospital ( Site 2502) - Herston
Recruitment hospital [4] 0 0
Icon Cancer Centre Hobart ( Site 2507) - Hobart
Recruitment hospital [5] 0 0
Austin Health ( Site 2501) - Melbourne
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
3084 - 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
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Dakota
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
South Dakota
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
Argentina
State/province [23] 0 0
Caba
Country [24] 0 0
Argentina
State/province [24] 0 0
Santa Fe
Country [25] 0 0
Argentina
State/province [25] 0 0
Buenos Aires
Country [26] 0 0
Austria
State/province [26] 0 0
Oberosterreich
Country [27] 0 0
Austria
State/province [27] 0 0
Steiermark
Country [28] 0 0
Austria
State/province [28] 0 0
Tirol
Country [29] 0 0
Austria
State/province [29] 0 0
Wien
Country [30] 0 0
Brazil
State/province [30] 0 0
Rio Grande Do Sul
Country [31] 0 0
Brazil
State/province [31] 0 0
Santa Catarina
Country [32] 0 0
Brazil
State/province [32] 0 0
Sao Paulo
Country [33] 0 0
Brazil
State/province [33] 0 0
Rio de Janeiro
Country [34] 0 0
Canada
State/province [34] 0 0
New Brunswick
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
France
State/province [37] 0 0
Ain
Country [38] 0 0
France
State/province [38] 0 0
Finistere
Country [39] 0 0
France
State/province [39] 0 0
Gironde
Country [40] 0 0
France
State/province [40] 0 0
Herault
Country [41] 0 0
France
State/province [41] 0 0
Seine-Maritime
Country [42] 0 0
France
State/province [42] 0 0
Somme
Country [43] 0 0
France
State/province [43] 0 0
Paris
Country [44] 0 0
Germany
State/province [44] 0 0
Baden-Wurttemberg
Country [45] 0 0
Germany
State/province [45] 0 0
Bayern
Country [46] 0 0
Germany
State/province [46] 0 0
Hessen
Country [47] 0 0
Germany
State/province [47] 0 0
Niedersachsen
Country [48] 0 0
Germany
State/province [48] 0 0
Nordrhein-Westfalen
Country [49] 0 0
Germany
State/province [49] 0 0
Berlin
Country [50] 0 0
Hungary
State/province [50] 0 0
Bacs-Kiskun
Country [51] 0 0
Hungary
State/province [51] 0 0
Baranya
Country [52] 0 0
Hungary
State/province [52] 0 0
Borsod-Abauj-Zemplen
Country [53] 0 0
Hungary
State/province [53] 0 0
Fejer
Country [54] 0 0
Hungary
State/province [54] 0 0
Gyor-Moson-Sopron
Country [55] 0 0
Hungary
State/province [55] 0 0
Hajdu-Bihar
Country [56] 0 0
Hungary
State/province [56] 0 0
Jasz-Nagykun-Szolnok
Country [57] 0 0
Hungary
State/province [57] 0 0
Pest
Country [58] 0 0
Hungary
State/province [58] 0 0
Somogy
Country [59] 0 0
Hungary
State/province [59] 0 0
Veszprem
Country [60] 0 0
Hungary
State/province [60] 0 0
Budapest
Country [61] 0 0
Italy
State/province [61] 0 0
Chieti
Country [62] 0 0
Italy
State/province [62] 0 0
Firenze
Country [63] 0 0
Italy
State/province [63] 0 0
Modena
Country [64] 0 0
Italy
State/province [64] 0 0
Roma
Country [65] 0 0
Japan
State/province [65] 0 0
Aichi
Country [66] 0 0
Japan
State/province [66] 0 0
Chiba
Country [67] 0 0
Japan
State/province [67] 0 0
Fukuoka
Country [68] 0 0
Japan
State/province [68] 0 0
Hyogo
Country [69] 0 0
Japan
State/province [69] 0 0
Ibaraki
Country [70] 0 0
Japan
State/province [70] 0 0
Miyagi
Country [71] 0 0
Japan
State/province [71] 0 0
Osaka
Country [72] 0 0
Japan
State/province [72] 0 0
Yamanashi
Country [73] 0 0
Japan
State/province [73] 0 0
Hiroshima
Country [74] 0 0
Japan
State/province [74] 0 0
Niigata
Country [75] 0 0
Japan
State/province [75] 0 0
Tokyo
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Chungbuk
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Kyonggi-do
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Seoul
Country [79] 0 0
Netherlands
State/province [79] 0 0
Gelderland
Country [80] 0 0
Netherlands
State/province [80] 0 0
Noord-Holland
Country [81] 0 0
Netherlands
State/province [81] 0 0
Utrecht
Country [82] 0 0
New Zealand
State/province [82] 0 0
Auckland
Country [83] 0 0
Norway
State/province [83] 0 0
Sor-Trondelag
Country [84] 0 0
Norway
State/province [84] 0 0
Vestfold
Country [85] 0 0
Norway
State/province [85] 0 0
Oslo
Country [86] 0 0
Poland
State/province [86] 0 0
Kujawsko-pomorskie
Country [87] 0 0
Poland
State/province [87] 0 0
Lodzkie
Country [88] 0 0
Poland
State/province [88] 0 0
Malopolskie
Country [89] 0 0
Poland
State/province [89] 0 0
Mazowieckie
Country [90] 0 0
Poland
State/province [90] 0 0
Slaskie
Country [91] 0 0
Poland
State/province [91] 0 0
Warminsko-mazurskie
Country [92] 0 0
Romania
State/province [92] 0 0
Cluj
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Chelyabinskaya Oblast
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Lipetskaya Oblast
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Moskva
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Sankt-Peterburg
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Sverdlovskaya Oblast
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Tatarstan, Respublika
Country [99] 0 0
Spain
State/province [99] 0 0
Madrid
Country [100] 0 0
Spain
State/province [100] 0 0
Valenciana, Comunitat
Country [101] 0 0
Spain
State/province [101] 0 0
Barcelona
Country [102] 0 0
Switzerland
State/province [102] 0 0
Geneve
Country [103] 0 0
Switzerland
State/province [103] 0 0
Zurich
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taipei
Country [105] 0 0
Taiwan
State/province [105] 0 0
Kaohsiung
Country [106] 0 0
Turkey
State/province [106] 0 0
Adana
Country [107] 0 0
Turkey
State/province [107] 0 0
Ankara
Country [108] 0 0
Turkey
State/province [108] 0 0
Istanbul
Country [109] 0 0
Turkey
State/province [109] 0 0
Izmir
Country [110] 0 0
Turkey
State/province [110] 0 0
Kayseri
Country [111] 0 0
Turkey
State/province [111] 0 0
Sakarya
Country [112] 0 0
Ukraine
State/province [112] 0 0
Dnipropetrovska Oblast
Country [113] 0 0
Ukraine
State/province [113] 0 0
Kharkivska Oblast
Country [114] 0 0
Ukraine
State/province [114] 0 0
Kirovohradska Oblast
Country [115] 0 0
Ukraine
State/province [115] 0 0
Kyivska Oblast
Country [116] 0 0
Ukraine
State/province [116] 0 0
Kyiv
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Bristol, City Of
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Camden
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Derbyshire
Country [120] 0 0
United Kingdom
State/province [120] 0 0
England
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Lancashire
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Leicestershire
Country [123] 0 0
United Kingdom
State/province [123] 0 0
London, City Of
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Norfolk
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Oxfordshire
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Darlington
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Northwood

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/NCT03924869