Clinical Trials /

Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo and Pembrolizumab as Maintenance Therapy

NCT04475939

Description:

This is a multicenter, randomized, double-blind, placebo-controlled study of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in participants with Stage IIIB or IV non-small cell lung cancer (NSCLC) (both squamous and non-squamous histology) who have achieved Stable disease (SD), Partial response (PR), or complete response (CR) following completion of platinum-based first-line induction chemotherapy with pembrolizumab. Eligible participants will be randomized to receive niraparib plus pembrolizumab or placebo plus pembrolizumab as maintenance therapy. The study's primary hypotheses are that 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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Placebo-controlled Study Comparing Niraparib Plus Pembrolizumab Versus Placebo and Pembrolizumab as Maintenance Therapy
  • 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 or IV Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 213400
  • NCT ID: NCT04475939

Conditions

  • Lung Cancer, Non-Small Cell

Interventions

DrugSynonymsArms
NiraparibParticipants receiving niraparib plus pembrolizumab
PembrolizumabParticipants receiving niraparib plus pembrolizumab
PlaceboParticipants receiving placebo plus pembrolizumab

Purpose

This is a multicenter, randomized, double-blind, placebo-controlled study of niraparib plus pembrolizumab versus placebo plus pembrolizumab as maintenance therapy in participants with Stage IIIB or IV non-small cell lung cancer (NSCLC) (both squamous and non-squamous histology) who have achieved Stable disease (SD), Partial response (PR), or complete response (CR) following completion of platinum-based first-line induction chemotherapy with pembrolizumab. Eligible participants will be randomized to receive niraparib plus pembrolizumab or placebo plus pembrolizumab as maintenance therapy. The study's primary hypotheses are that 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).

Trial Arms

NameTypeDescriptionInterventions
Participants receiving niraparib plus pembrolizumabExperimentalParticipants will be administered pembrolizumab at a dose of 200 milligrams (mg) via an intravenous infusion over 30 minutes on Day 1 of each treatment cycle (each cycle of 21 days). Niraparib will be administered orally once a day, continuously throughout the 21-day cycle starting on Cycle 1 (Day 1).
  • Niraparib
  • Pembrolizumab
Participants receiving placebo plus pembrolizumabPlacebo ComparatorParticipants will be administered pembrolizumab at a dose of 200 mg via an intravenous infusion over 30 minutes on Day 1 of each treatment cycle (each cycle of 21 days). Placebo will be administered orally once a day, continuously throughout the 21-day cycle starting on Cycle 1 (Day 1).
  • Pembrolizumab
  • Placebo

Eligibility 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 metastatic
             (Stage IV) NSCLC.

          -  Has completed at least 4 but no more than 6 cycles of platinum-based first-line
             induction chemotherapy with pembrolizumab.

          -  Has SD, PR, or CR of the NSCLC after completion of 4 to 6 cycles of pembrolizumab plus
             platinum-based first line induction chemotherapy.

          -  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.

        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) and/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 BM, or radiologic
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) by BICR using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Time to progression (TTP)
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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.
Measure:PFS by investigator assessment
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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.
Measure:PFS by programmed cell death-ligand 1 (PD-L1) status
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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%).
Measure:OS by PD-L1 status
Time Frame:Up to approximately 5 years
Safety Issue:
Description: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%).
Measure:Time to Deterioration (TTD) in Lung Symptoms
Time Frame:Up to approximately 3 years
Safety Issue:
Description:TTD is defined as the time from randomization to meaningful deterioration on a composite endpoint of dyspnea, chest pain, and cough on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 13-item lung cancer-specific module (EORTC QLQ-LC13).
Measure: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)
Safety Issue:
Description:EORTC QLQ-C30 is a validated questionnaire to assess overall health-related quality of life in participants with cancer and contains 30 questions including multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/quality of life scale (GHS/QOL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). The QLQ-C30 employs a week recall period for all items and a 4-point scale for the functional and symptom scales/items with response categories "Not at all", "A little", "Quite a bit" and "Very much". The two items assessing GHS/QOL utilize a 7-point scale ranging from 1 ("Very Poor") to 7 ("Excellent"). Scores are averaged, and transformed to a 0-100 scale. A higher score on functional scales represents better function, and on symptom scales represents more severe symptoms.
Measure: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)
Safety Issue:
Description:The EORTC QLQ-LC13 is a clinically valid and useful tool for assessing disease- and treatment-specific symptoms in lung cancer participants. It is a lung cancer-specific questionnaire module designed to supplement the EORTC QLQ-C30. The measures in the lung cancer questionnaire module assess both lung cancer-associated symptoms, such as coughing, shortness of breath (dyspnea), hemoptysis, and pain, as well as side effects from conventional chemo- and radiotherapy, such as hair loss, neuropathy, sore mouth, and dysphagia.
Measure: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
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant temporally associated with the use of study treatment whether or not related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose; results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability or incapacity or is a congenital anomaly or birth defect or any other situation that require medical or scientific judgment. Selected non-serious AEs and SAEs are also known as AESI. Non-serious AEs, SAEs and AESIs will be assessed.
Measure:Number of participants discontinuing study treatment due to AEs
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Number of participants discontinuing the treatment due to AEs will be assessed.
Measure:Number of participants with niraparib/placebo and pembrolizumab dose interruptions due to AEs
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Number of participants with dose interruptions due to AEs will be assessed.
Measure:Number of participants with dose reductions due to AEs
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Number of participants with dose reductions due to AEs will be assessed.
Measure:Number of participants with clinically significant changes in hematology parameters
Time Frame:Baseline and until 90 days after last treatment dose (up to approximately 3 years)
Safety Issue:
Description:Blood samples will be collected for the assessment of hematology parameters.
Measure:Number of participants with clinically significant changes in clinical chemistry parameters
Time Frame:Baseline and until 90 days after last treatment dose (up to approximately 3 years)
Safety Issue:
Description:Blood samples will be collected for the assessment of chemistry parameters.
Measure:Number of participants with abnormal urine parameters
Time Frame:At Baseline
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of specific gravity, occult blood, glucose, ketones, protein, nitrite, leukocyte esterase, bilirubin, urobilinogen in urine.
Measure:Number of participants with change from baseline in Thyroid Function Parameters
Time Frame:Baseline and until 90 days after last treatment dose (up to approximately 3 years)
Safety Issue:
Description:Blood samples will be collected for the assessment of thyroid parameters.
Measure:Apparent total oral clearance of niraparib in plasma after oral administration (CL/F)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for pharmacokinetic (PK) analysis of niraparib when given in combination with pembrolizumab.
Measure:Apparent central (Vc/F) and peripheral (Vp/F) volume of niraparib in plasma after oral administration
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for PK analysis of niraparib when given in combination with pembrolizumab.
Measure:Area under the plasma concentration-time curve (AUC) of niraparib
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for PK analysis of niraparib when given in combination with pembrolizumab.
Measure:Maximum concentration (Cmax) and Minimum concentration (Cmin) of niraparib at steady state
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for PK analysis of niraparib when given in combination with pembrolizumab.
Measure:Dose normalized Cmax and Cmin of niraparib
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for PK analysis of niraparib when given in combination with pembrolizumab.
Measure:Average Concentration (Cave) and Dose-normalized Concentration (Cave) of niraparib at steady state
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Blood samples will be collected at indicated time points for PK analysis of niraparib when given in combination with pembrolizumab.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Non-Small Cell Lung Cancer
  • Niraparib
  • Pembrolizumab
  • Maintenance therapy
  • Chemotherapy
  • Platinum-based

Last Updated

November 25, 2020