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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03066778




Registration number
NCT03066778
Ethics application status
Date submitted
23/02/2017
Date registered
28/02/2017

Titles & IDs
Public title
A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)
Scientific title
A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNOTE-604)
Secondary ID [1] 0 0
173744
Secondary ID [2] 0 0
3475-604
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer (SCLC) 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 - Pembrolizumab
Treatment: Drugs - Normal saline solution
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Etoposide

Experimental: Pembrolizumab+EP - During each 21-day cycle, participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an area under the plasma drug concentration-time curve \[AUC\] 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1). Participants who stop pembrolizumab as a result of obtaining a response of stable disease (SD), partial response (PR), complete response (CR) or those who stop after receiving pembrolizumab for 24 months for reasons other than disease progression or intolerability, are eligible for up to an additional 1 year of treatment after progressive disease if they meet the criteria for retreatment.

Active comparator: Placebo+EP - During each 21-day cycle, participants receive placebo (normal saline solution) IV on Day 1 PLUS etoposide 100 mg/m\^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum therapy (carboplatin titrated to an AUC 5 IV on Day 1 OR cisplatin 75 mg/m\^2 IV on Day 1).


Treatment: Other: Pembrolizumab
IV infusion on Day 1 of each cycle prior to chemotherapy

Treatment: Drugs: Normal saline solution
IV infusion on Day 1 of each cycle prior to chemotherapy

Treatment: Drugs: Carboplatin
IV infusion on Day 1 of each cycle

Treatment: Drugs: Cisplatin
IV infusion on Day 1 of each cycle

Treatment: Drugs: Etoposide
IV infusion on Days 1, 2 and 3 of each 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
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 30.5 months
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 30.5 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 30.5 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Timepoint [2] 0 0
Up to approximately 30.5 months
Secondary outcome [3] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 30.5 months
Secondary outcome [4] 0 0
Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 26 months
Secondary outcome [5] 0 0
Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03)
Timepoint [5] 0 0
Up to approximately 30.5 months
Secondary outcome [6] 0 0
Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [6] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 18
Secondary outcome [7] 0 0
Change From Baseline at Week 12 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [7] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 12
Secondary outcome [8] 0 0
Change From Baseline at Week 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
Timepoint [8] 0 0
Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 24
Secondary outcome [9] 0 0
Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13)
Timepoint [9] 0 0
Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 27 months)

Eligibility
Key inclusion criteria
* Has a documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration of a defined lesion. Participants who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample.
* Has extensive-stage disease defined as Stage IV (T any, N any, M 1a/b) by the American Joint Committee on Cancer (AJCC), Seventh Edition
* Has =1 lesion that meets the criteria for measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology assessment
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Has a life expectancy of =3 months
* Has adequate organ function
* Female and male participants of childbearing potential must be willing to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of chemotherapeutic agents
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has received prior systemic therapy for the treatment of SCLC
* Is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem
* Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study. (Prophylactic cranial irradiation will be possible for those participants with stable disease or better at the completion of the 4 cycles of chemotherapy with or without pembrolizumab.)
* Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following:
* Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) =14 days prior to the first dose of study treatment,
* Has no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed =3 weeks after pre-treatment brain imaging, and
* Is neurologically stable without the need for steroids for =7 days before first dose of study treatment.
* Has had major surgery within 3 weeks prior to receiving the first dose of study treatment or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study treatment.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has a known history of interstitial lung disease
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
* Has a known history of, or active, neurologic paraneoplastic syndrome
* Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
* Has a history of a severe hypersensitivity reaction to treatment with another monoclonal antibody
* Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study treatment
* Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Has received a live vaccine within 30 days prior to the first dose of study treatment
* Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
* Has severe hypersensitivity (Grade =3) to pembrolizumab and/or any of its excipients
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has a known history of active TB (Bacillus Tuberculosis)
* Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
* 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 treatment through and up to 180 days after last dose of chemotherapeutic agents

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/09/2021
Sample size
Target
Accrual to date
Final
453
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Blacktown Hospital ( Site 0004) - Blacktown
Recruitment hospital [2] 0 0
Southern Medical Day Care Centre ( Site 0001) - Wollongong
Recruitment hospital [3] 0 0
St John of God ( Site 0006) - Murdoch
Recruitment hospital [4] 0 0
Lyell McEwin Hospital ( Site 0002) - Elizabeth Vale
Recruitment hospital [5] 0 0
St Vincents Hospital Melbourne ( Site 0005) - Fitzroy
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
6150 - Murdoch
Recruitment postcode(s) [4] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Mississippi
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
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
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Nova Scotia
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
Chile
State/province [21] 0 0
Region Metropolitana
Country [22] 0 0
Chile
State/province [22] 0 0
Santiago
Country [23] 0 0
Chile
State/province [23] 0 0
Talca
Country [24] 0 0
France
State/province [24] 0 0
Lille
Country [25] 0 0
France
State/province [25] 0 0
Limoges
Country [26] 0 0
France
State/province [26] 0 0
Nantes
Country [27] 0 0
France
State/province [27] 0 0
Nice
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Reims
Country [30] 0 0
France
State/province [30] 0 0
Toulouse
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Dresden
Country [33] 0 0
Germany
State/province [33] 0 0
Duesseldorf
Country [34] 0 0
Germany
State/province [34] 0 0
Gera
Country [35] 0 0
Germany
State/province [35] 0 0
Hamburg
Country [36] 0 0
Germany
State/province [36] 0 0
Heidelberg
Country [37] 0 0
Germany
State/province [37] 0 0
Marburg
Country [38] 0 0
Germany
State/province [38] 0 0
Tuebingen
Country [39] 0 0
Hungary
State/province [39] 0 0
Pest
Country [40] 0 0
Hungary
State/province [40] 0 0
Budapest
Country [41] 0 0
Hungary
State/province [41] 0 0
Farkasgyepu
Country [42] 0 0
Hungary
State/province [42] 0 0
Gyor
Country [43] 0 0
Hungary
State/province [43] 0 0
Szekesfehervar
Country [44] 0 0
Hungary
State/province [44] 0 0
Szolnok
Country [45] 0 0
Hungary
State/province [45] 0 0
Zalaegerszeg
Country [46] 0 0
Ireland
State/province [46] 0 0
Dublin
Country [47] 0 0
Israel
State/province [47] 0 0
Beer Sheva
Country [48] 0 0
Israel
State/province [48] 0 0
Haifa
Country [49] 0 0
Israel
State/province [49] 0 0
Kfar Saba
Country [50] 0 0
Israel
State/province [50] 0 0
Petah Tikva
Country [51] 0 0
Israel
State/province [51] 0 0
Ramat-Gan
Country [52] 0 0
Japan
State/province [52] 0 0
Aichi
Country [53] 0 0
Japan
State/province [53] 0 0
Chiba
Country [54] 0 0
Japan
State/province [54] 0 0
Ehime
Country [55] 0 0
Japan
State/province [55] 0 0
Fukuoka
Country [56] 0 0
Japan
State/province [56] 0 0
Hyogo
Country [57] 0 0
Japan
State/province [57] 0 0
Kanagawa
Country [58] 0 0
Japan
State/province [58] 0 0
Miyagi
Country [59] 0 0
Japan
State/province [59] 0 0
Osaka
Country [60] 0 0
Japan
State/province [60] 0 0
Shizuoka
Country [61] 0 0
Japan
State/province [61] 0 0
Yamaguchi
Country [62] 0 0
Japan
State/province [62] 0 0
Hiroshima
Country [63] 0 0
Japan
State/province [63] 0 0
Niigata
Country [64] 0 0
Japan
State/province [64] 0 0
Tokyo
Country [65] 0 0
Japan
State/province [65] 0 0
Wakayama
Country [66] 0 0
Korea, Republic of
State/province [66] 0 0
Busan
Country [67] 0 0
Korea, Republic of
State/province [67] 0 0
Goyang-si
Country [68] 0 0
Korea, Republic of
State/province [68] 0 0
Seoul
Country [69] 0 0
New Zealand
State/province [69] 0 0
Christchurch
Country [70] 0 0
Poland
State/province [70] 0 0
Mazowieckie
Country [71] 0 0
Poland
State/province [71] 0 0
Konin
Country [72] 0 0
Poland
State/province [72] 0 0
Krakow
Country [73] 0 0
Poland
State/province [73] 0 0
Lublin
Country [74] 0 0
Poland
State/province [74] 0 0
Poznan
Country [75] 0 0
Poland
State/province [75] 0 0
Torun
Country [76] 0 0
Poland
State/province [76] 0 0
Warszawa
Country [77] 0 0
Poland
State/province [77] 0 0
Wroclaw
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Belgorod
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Moscow
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Pyatigorsk
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Saint Petersburg
Country [82] 0 0
Spain
State/province [82] 0 0
Gran Canaria
Country [83] 0 0
Spain
State/province [83] 0 0
A Coruna
Country [84] 0 0
Spain
State/province [84] 0 0
Barcelona
Country [85] 0 0
Spain
State/province [85] 0 0
Jaen
Country [86] 0 0
Spain
State/province [86] 0 0
Madrid
Country [87] 0 0
Spain
State/province [87] 0 0
Valencia
Country [88] 0 0
Switzerland
State/province [88] 0 0
Chur
Country [89] 0 0
Switzerland
State/province [89] 0 0
Lausanne
Country [90] 0 0
Switzerland
State/province [90] 0 0
Zuerich
Country [91] 0 0
Taiwan
State/province [91] 0 0
Kaohsiung
Country [92] 0 0
Taiwan
State/province [92] 0 0
Taichung
Country [93] 0 0
Taiwan
State/province [93] 0 0
Tainan
Country [94] 0 0
Taiwan
State/province [94] 0 0
Taipei
Country [95] 0 0
Turkey
State/province [95] 0 0
Bornova
Country [96] 0 0
Turkey
State/province [96] 0 0
Adana
Country [97] 0 0
Turkey
State/province [97] 0 0
Ankara
Country [98] 0 0
Turkey
State/province [98] 0 0
Edirne
Country [99] 0 0
Turkey
State/province [99] 0 0
Istanbul
Country [100] 0 0
Turkey
State/province [100] 0 0
Izmir
Country [101] 0 0
Turkey
State/province [101] 0 0
Kocaeli
Country [102] 0 0
Turkey
State/province [102] 0 0
Malatya
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Birmingham
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Leeds
Country [105] 0 0
United Kingdom
State/province [105] 0 0
London
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Maidstone
Country [107] 0 0
United Kingdom
State/province [107] 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?




Results publications and other study-related documents

TypeCitations or Other Details
Journal Rudin CM, Awad MM, Navarro A, Gottfried M, Peters ... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03066778