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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04475939




Registration number
NCT04475939
Ethics application status
Date submitted
14/07/2020
Date registered
17/07/2020

Titles & IDs
Public title
Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-small Cell Lung Cancer
Scientific title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants Whose Disease Has Remained Stable or Responded to First-Line Platinum Based Chemotherapy With Pembrolizumab for Stage IIIB/IIIC or IV Non-Small Cell Lung Cancer (ZEAL-1L)
Secondary ID [1] 0 0
213400
Universal Trial Number (UTN)
Trial acronym
ZEAL-1L
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Cancer, Non-Small Cell 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: Drugs - Niraparib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: Participants receiving niraparib plus pembrolizumab - Eligible participants will receive niraparib along with pembrolizumab.

Placebo comparator: Participants receiving placebo plus pembrolizumab - Eligible participants will receive matching placebo along with pembrolizumab.


Treatment: Drugs: Niraparib
Niraparib will be administered

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered

Treatment: Drugs: Placebo
Matching placebo will be administered

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 in overall population
Timepoint [1] 0 0
Up to approximately 3 years
Primary outcome [2] 0 0
Overall survival (OS) in overall population
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
PFS assessed by BICR using RECIST v 1.1 in non-squamous histology (NSQ) population
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [2] 0 0
PFS assessed by BICR using RECIST v 1.1 in complete and partial response (CR/PR) population
Timepoint [2] 0 0
Up to approximately 3 years
Secondary outcome [3] 0 0
OS in NSQ population
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
OS in CR/PR population
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
Time to progression (TTP)
Timepoint [5] 0 0
Up to approximately 3 years
Secondary outcome [6] 0 0
PFS by investigator assessment using RECIST v1.1
Timepoint [6] 0 0
Up to approximately 3 years
Secondary outcome [7] 0 0
CNS PFS as assessed by BICR using RANO-BM
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
PFS as assessed by BICR using RECIST v1.1 by programmed cell death-ligand 1 (PD-L1) status
Timepoint [8] 0 0
Up to approximately 3 years
Secondary outcome [9] 0 0
OS by PD-L1 status
Timepoint [9] 0 0
Up to approximately 5 years
Secondary outcome [10] 0 0
Time to Deterioration (TTD) in Lung Symptoms
Timepoint [10] 0 0
Up to approximately 3 years
Secondary outcome [11] 0 0
Change from Baseline in Health-related quality of life (HRQoL) and symptoms by EORTC QLQ-C30-item Core module (EORTC QLQ-C30) (Scores on a scale)
Timepoint [11] 0 0
Baseline, Day 1 in Cycles 1, 2, 3, 4, 5 (Each cycle is of 21 Days); thereafter every 2 cycles until 90 days after last treatment dose (up to approximately 3 years)
Secondary outcome [12] 0 0
Change from Baseline in HRQoL and symptoms by EORTC QLQ-LC13 (Scores on a scale)
Timepoint [12] 0 0
Baseline, Day 1 in Cycles 1, 2, 3, 4, 5 (Each cycle is of 21 Days); thereafter every 2 cycles until 90 days after last treatment dose (up to approximately 3 years)
Secondary outcome [13] 0 0
Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)
Timepoint [13] 0 0
Up to approximately 3 years
Secondary outcome [14] 0 0
Plasma concentrations of niraparib
Timepoint [14] 0 0
Up to approximately 3 years

Eligibility
Key inclusion criteria
Inclusion criteria:

* Participant must be >=18 years of age.
* Has a histologically or cytologically confirmed diagnosis of NSCLC without known targetable driver alteration (either non-squamous or squamous histology; mixed histology is allowed for which an approved targeted therapy is available in the 1L induction/maintenance therapy setting).
* Has advanced (Stage IIIB or Stage IIIC, not amenable to definitive chemoradiotherapy) or metastatic (Stage IV) or metastatic (Stage IV) NSCLC.
* Has completed at least 4 but no more than 6 cycles of standard of care first-line platinum-based induction chemotherapy with pembrolizumab.
* Has SD, PR, or CR of the NSCLC per Investigator's assessment after completion of 4 to 6 cycles of standard of care first-line platinum-based induction chemotherapy with pembrolizumab.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Has a life expectancy of at least 12 weeks.
* Has adequate organ and bone marrow function.
* Must submit tumor specimens.
* Must be able to swallow and retain orally administered study treatment.
* A female is eligible to participate if she is not pregnant or breastfeeding, and must follow contraceptive guidance during the treatment period and 180 days afterwards.
* A male is eligible to participate if he agrees to contraceptive guidance and refrains from sperm donation during the intervention period and for at least 90 days after the last dose of study treatment.
* Is able to understand the study procedures and agrees to participate in the study by providing written informed consent. Participants must be informed that their participation is voluntary. Participants will be required to sign a statement of informed consent to participate in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Has mixed small cell lung cancer or sarcomatoid variant NSCLC.
* Has received prior Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor(s) in prior lines of treatment.
* Has systolic blood pressure (BP) >140 millimeters of mercury (mmHg) or diastolic BP >90 mmHg.
* Has any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
* Has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiographic signs of CNS hemorrhage.
* Has received colony-stimulating factors (granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment.
* Has an active or previously documented autoimmune or inflammatory disorder.
* Is receiving chronic systemic steroids (prednisone >20 mg per day) other than intermittent use of bronchodilators, inhaled steroids, or local steroid.
* Has other active concomitant malignancy that warrants systemic, biologic, or hormonal therapy.
* Is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment and/or for up to 180 days after the last dose of study treatment.
* Has a known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
* Has a known history of active tuberculosis.
* Has current active pneumonitis within 90 days of planned start of the study or a known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis requiring steroid treatment.

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 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
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,TAS,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Blacktown
Recruitment hospital [2] 0 0
GSK Investigational Site - Hobart
Recruitment hospital [3] 0 0
GSK Investigational Site - Ballarat
Recruitment hospital [4] 0 0
GSK Investigational Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
3350 - Ballarat
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
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
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Argentina
State/province [17] 0 0
Río Negro
Country [18] 0 0
Argentina
State/province [18] 0 0
Santa Fe
Country [19] 0 0
Argentina
State/province [19] 0 0
Ciudad Autónoma de Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Cordoba
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Edegem
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Roeselaere
Country [25] 0 0
Brazil
State/province [25] 0 0
Espírito Santo
Country [26] 0 0
Brazil
State/province [26] 0 0
Minas Gerais
Country [27] 0 0
Brazil
State/province [27] 0 0
Paraná
Country [28] 0 0
Brazil
State/province [28] 0 0
Rio Grande Do Sul
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Brazil
State/province [30] 0 0
São Paulo
Country [31] 0 0
Bulgaria
State/province [31] 0 0
Panagyurishte
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Pleven
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Plovdiv
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Ruse
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Sofia
Country [36] 0 0
Chile
State/province [36] 0 0
Región De La Araucania
Country [37] 0 0
Chile
State/province [37] 0 0
Región Metro De Santiago
Country [38] 0 0
Colombia
State/province [38] 0 0
Bogota
Country [39] 0 0
Colombia
State/province [39] 0 0
Monteria
Country [40] 0 0
France
State/province [40] 0 0
Brest cedex
Country [41] 0 0
France
State/province [41] 0 0
Créteil cedex
Country [42] 0 0
France
State/province [42] 0 0
Grenoble cedex 9
Country [43] 0 0
France
State/province [43] 0 0
Lille cedex
Country [44] 0 0
France
State/province [44] 0 0
Nantes cedex 1
Country [45] 0 0
France
State/province [45] 0 0
Paris
Country [46] 0 0
France
State/province [46] 0 0
Rennes Cedex 9
Country [47] 0 0
France
State/province [47] 0 0
Strasbourg
Country [48] 0 0
France
State/province [48] 0 0
Toulon cedex
Country [49] 0 0
France
State/province [49] 0 0
Toulouse cedex 9
Country [50] 0 0
Germany
State/province [50] 0 0
Baden-Wuerttemberg
Country [51] 0 0
Germany
State/province [51] 0 0
Bayern
Country [52] 0 0
Germany
State/province [52] 0 0
Hessen
Country [53] 0 0
Germany
State/province [53] 0 0
Niedersachsen
Country [54] 0 0
Germany
State/province [54] 0 0
Nordrhein-Westfalen
Country [55] 0 0
Germany
State/province [55] 0 0
Sachsen-Anhalt
Country [56] 0 0
Germany
State/province [56] 0 0
Schleswig-Holstein
Country [57] 0 0
Germany
State/province [57] 0 0
Thueringen
Country [58] 0 0
Germany
State/province [58] 0 0
Berlin
Country [59] 0 0
Germany
State/province [59] 0 0
Hamburg
Country [60] 0 0
Greece
State/province [60] 0 0
Athens
Country [61] 0 0
Greece
State/province [61] 0 0
Heraklion,Crete
Country [62] 0 0
Greece
State/province [62] 0 0
Larisa
Country [63] 0 0
Greece
State/province [63] 0 0
Maroussi
Country [64] 0 0
Greece
State/province [64] 0 0
N. Faliro
Country [65] 0 0
Greece
State/province [65] 0 0
Patra
Country [66] 0 0
Greece
State/province [66] 0 0
Rio/Patras
Country [67] 0 0
Greece
State/province [67] 0 0
Thessaloniki
Country [68] 0 0
Hungary
State/province [68] 0 0
Budapest
Country [69] 0 0
Hungary
State/province [69] 0 0
Gyöngyös
Country [70] 0 0
Hungary
State/province [70] 0 0
Tatabánya
Country [71] 0 0
Hungary
State/province [71] 0 0
Törökbálint
Country [72] 0 0
Hungary
State/province [72] 0 0
Zalaegerszeg
Country [73] 0 0
Ireland
State/province [73] 0 0
Cork
Country [74] 0 0
Ireland
State/province [74] 0 0
Dublin
Country [75] 0 0
Italy
State/province [75] 0 0
Campania
Country [76] 0 0
Italy
State/province [76] 0 0
Friuli-Venezia-Giulia
Country [77] 0 0
Italy
State/province [77] 0 0
Lazio
Country [78] 0 0
Italy
State/province [78] 0 0
Lombardia
Country [79] 0 0
Italy
State/province [79] 0 0
Piemonte
Country [80] 0 0
Italy
State/province [80] 0 0
Puglia
Country [81] 0 0
Italy
State/province [81] 0 0
Sicilia
Country [82] 0 0
Italy
State/province [82] 0 0
Toscana
Country [83] 0 0
Italy
State/province [83] 0 0
Veneto
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Gyeonggi-do
Country [85] 0 0
Korea, Republic of
State/province [85] 0 0
Seongnam-si, Gyeonggi-do
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Seoul
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Suwon-Si
Country [88] 0 0
Mexico
State/province [88] 0 0
Ciudad De Mexico
Country [89] 0 0
Mexico
State/province [89] 0 0
Nuevo León
Country [90] 0 0
Mexico
State/province [90] 0 0
Mexico City
Country [91] 0 0
Mexico
State/province [91] 0 0
Puebla
Country [92] 0 0
Netherlands
State/province [92] 0 0
Amersfoort
Country [93] 0 0
Netherlands
State/province [93] 0 0
Amsterdam
Country [94] 0 0
Netherlands
State/province [94] 0 0
Den Bosch
Country [95] 0 0
Netherlands
State/province [95] 0 0
Enschede
Country [96] 0 0
Netherlands
State/province [96] 0 0
Maastricht
Country [97] 0 0
Netherlands
State/province [97] 0 0
Utrecht
Country [98] 0 0
Netherlands
State/province [98] 0 0
Zwolle
Country [99] 0 0
Norway
State/province [99] 0 0
Drammen
Country [100] 0 0
Norway
State/province [100] 0 0
Lørenskog
Country [101] 0 0
Norway
State/province [101] 0 0
Oslo
Country [102] 0 0
Peru
State/province [102] 0 0
Lima
Country [103] 0 0
Poland
State/province [103] 0 0
Bialystok
Country [104] 0 0
Poland
State/province [104] 0 0
Lodz
Country [105] 0 0
Poland
State/province [105] 0 0
Olsztyn
Country [106] 0 0
Romania
State/province [106] 0 0
Bucharest
Country [107] 0 0
Romania
State/province [107] 0 0
Bucuresti
Country [108] 0 0
Romania
State/province [108] 0 0
Cluj-Napoca
Country [109] 0 0
Romania
State/province [109] 0 0
Craiova
Country [110] 0 0
Romania
State/province [110] 0 0
Iasi
Country [111] 0 0
Romania
State/province [111] 0 0
Satu Mare
Country [112] 0 0
Romania
State/province [112] 0 0
Timisoara
Country [113] 0 0
Russian Federation
State/province [113] 0 0
Moscow
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Nizhniy Novgorod
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Omsk
Country [116] 0 0
Russian Federation
State/province [116] 0 0
Saint-Petersburg
Country [117] 0 0
Russian Federation
State/province [117] 0 0
St. Petersburg
Country [118] 0 0
Spain
State/province [118] 0 0
Barcelona
Country [119] 0 0
Spain
State/province [119] 0 0
Cordoba
Country [120] 0 0
Spain
State/province [120] 0 0
Girona
Country [121] 0 0
Spain
State/province [121] 0 0
La Coruña
Country [122] 0 0
Spain
State/province [122] 0 0
Las Palmas De Gran Canaria
Country [123] 0 0
Spain
State/province [123] 0 0
Madrid
Country [124] 0 0
Spain
State/province [124] 0 0
Majadahonda (Madrid)
Country [125] 0 0
Spain
State/province [125] 0 0
Málaga
Country [126] 0 0
Spain
State/province [126] 0 0
Pamplona
Country [127] 0 0
Spain
State/province [127] 0 0
Santander
Country [128] 0 0
Spain
State/province [128] 0 0
Zaragoza
Country [129] 0 0
Sweden
State/province [129] 0 0
Gävle
Country [130] 0 0
Sweden
State/province [130] 0 0
Stockholm
Country [131] 0 0
Sweden
State/province [131] 0 0
Uppsala
Country [132] 0 0
Switzerland
State/province [132] 0 0
Lausanne
Country [133] 0 0
Turkey
State/province [133] 0 0
Ankara
Country [134] 0 0
Turkey
State/province [134] 0 0
Edirne
Country [135] 0 0
Turkey
State/province [135] 0 0
Istanbul
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Middlesex
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Bournemouth
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Dundee
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Oxford
Country [140] 0 0
United Kingdom
State/province [140] 0 0
Wrexham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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?
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk.com/en-gb/innovation/trials/data-transparency/


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.