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Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo Plus Pembrolizumab as Maintenance Therapy in Participants With Advanced/Metastatic Non-small Cell Lung Cancer (ZEAL-1L)

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ClinicalTrials.gov Identifier: NCT04475939
Recruitment Status : Recruiting
First Posted : July 17, 2020
Last Update Posted : October 5, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This is a multicenter, randomized, double-blind, placebo-controlled study of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in participants with advanced or metastatic non-small cell lung cancer (NSCLC) who have achieved stable disease (SD), partial response (PR), or complete response (CR) following completion of standard of care first-line platinum-based induction chemotherapy with pembrolizumab. The primary hypotheses are: participants with confirmed diagnosis of NSCLC could benefit from niraparib plus pembrolizumab versus placebo plus pembrolizumab with respect to Progression-free survival (PFS) and Overall survival (OS).

Condition or disease Intervention/treatment Phase
Lung Cancer, Non-Small Cell Drug: Niraparib Drug: Pembrolizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 650 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicenter, randomized, double-blind, placebo-controlled study.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The participant, Investigator, study staff, and the Sponsor study team will be blinded.
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : October 26, 2020
Estimated Primary Completion Date : August 28, 2024
Estimated Study Completion Date : October 28, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Participants receiving niraparib plus pembrolizumab
Eligible participants will receive niraparib along with pembrolizumab.
Drug: Niraparib
Niraparib will be administered

Drug: Pembrolizumab
Pembrolizumab will be administered

Placebo Comparator: Participants receiving placebo plus pembrolizumab
Eligible participants will receive matching placebo along with pembrolizumab.
Drug: Pembrolizumab
Pembrolizumab will be administered

Drug: Placebo
Matching placebo will be administered




Primary Outcome Measures :
  1. Progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 [ Time Frame: Up to approximately 3 years ]
    PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by BICR or death from any cause in the absence of progression, whichever occurs first.

  2. Overall survival (OS) [ Time Frame: Up to approximately 5 years ]
    OS is defined as the time from randomization to the date of death due to any cause.


Secondary Outcome Measures :
  1. Time to progression (TTP) [ Time Frame: Up to approximately 3 years ]
    TTP in the Central nervous system (CNS) is defined as the time from the date of randomization until the earliest date of documented PD in the CNS, based on BICR assessment using response assessment in neuro-oncology brain metastases (RANO-BM) criteria.

  2. PFS by investigator assessment [ Time Frame: Up to approximately 3 years ]
    PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by the Investigator using RECIST v1.1 or death from any cause in the absence of progression, whichever occurs first.

  3. PFS by programmed cell death-ligand 1 (PD-L1) status [ Time Frame: Up to approximately 3 years ]
    PFS is defined as the time from the date of randomization to the date of first radiographic progression as determined by BICR using RECIST v1.1 or death from any cause in the absence of progression, whichever occurs first. PFS will be assessed by PD-L1 status (PD-L1 tumor cells [TCs] less than [<]1% versus more than or equal to [>=]1%).

  4. OS by PD-L1 status [ Time Frame: Up to approximately 5 years ]
    OS is defined as the time from randomization to the date of death due to any cause. OS will be assessed by PD-L1 status (PD-L1-TCs <1% versus >=1%).

  5. Time to Deterioration (TTD) in Lung Symptoms [ Time Frame: Up to approximately 3 years ]
    TTD is defined as the time from randomization to meaningful deterioration as measured by (EORTC QLQ-LC13) questionnaire.

  6. Change from Baseline in Health-related quality of life (HRQoL) and symptoms by EORTC 30-item Core module (EORTC QLQ-C30) (Scores on a scale) [ Time Frame: 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) ]
    EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer.

  7. Change from Baseline in HRQoL and symptoms by EORTC QLQ-LC13 (Scores on a scale) [ Time Frame: 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) ]
    The EORTC QLQ-LC13 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer participants.

  8. Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [ Time Frame: Up to approximately 3 years ]
    AEs, SAEs and AESIs will be collected.

  9. Plasma concentrations of niraparib [ Time Frame: Up to approximately 3 years ]
    Blood samples will be collected to assess the plasma concentrations of niraparib.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  • Has advanced (Stage IIIB not amenable to definitive chemoradiotherapy or Stage IIIC) 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 180 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04475939


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04475939    
Other Study ID Numbers: 213400
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Niraparib
Pembrolizumab
Maintenance therapy
Chemotherapy
Platinum-based
Additional relevant MeSH terms:
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Niraparib
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action