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Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03003962
Recruitment Status : Active, not recruiting
First Posted : December 28, 2016
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
This is a randomized, open-label, multi-center Phase III study to determine the efficacy and safety of durvalumab versus platinum-based SoC chemotherapy in the first-line treatment of advanced NSCLC in patients who are epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type and with PD-L1 high expression (PEARL)

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Carcinoma NSCLC Drug: Durvalumab (MEDI4736) Drug: Paclitaxel + carboplatin Drug: Gemcitabine + cisplatin Drug: Gemcitabine + carboplatin Drug: Pemetrexed + cisplatin Drug: Pemetrexed + carboplatin Phase 3

Detailed Description:
Patients with stage IV NSCLC will be randomized in a 1:1 ratio to 2 treatment arms (durvalumab or SOC therapy). The dual primary objectives of this study are to assess the efficacy of durvalumab versus SoC in terms of OS (Overall Survival) in all randomized patients and in patients who are at low risk of EM (early mortality)
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 669 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Open-Label, Multi-Center Study of Durvalumab (MEDI4736) Versus Standard of Care (SoC) Platinum-Based Chemotherapy as First Line Treatment in Patients With PD-L1-High Expression Advanced Non Small-Cell Lung Cancer
Actual Study Start Date : January 2, 2017
Estimated Primary Completion Date : January 25, 2021
Estimated Study Completion Date : January 25, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1: Durvalumab
Anti-PD-L1 monoclonal Antibody monotherapy
 Drug: Durvalumab (MEDI4736)
Anti-PD-L1 monoclonal Antibody monotherapy
Active Comparator: Arm 2: Standard of Care
Standard of Care Platinum-Based chemotherapy
 Drug: Paclitaxel + carboplatin
Chemotherapy Agents
Other Name: Platinum based Standard of Care Chemotherapy

Drug: Gemcitabine + cisplatin
Chemotherapy Agents
Other Name: Platinum based Standard of Care Chemotherapy

Drug: Gemcitabine + carboplatin
Chemotherapy Agents
Other Name: Platinum based Standard of Care Chemotherapy

Drug: Pemetrexed + cisplatin
Chemotherapy Agent
Other Name: Platinum based Standard of Care Chemotherapy

Drug: Pemetrexed + carboplatin
Chemotherapy Agent
Other Name: Platinum based Standard of Care Chemotherapy


Outcome Measures
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Primary Outcome Measures :
  1. The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in all randomized patients [ Time Frame: 4 years ]
  2. The efficacy of Durvalumab therapy compared to SoC in terms of OS in patients who are at low risk of early mortality (EM) [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. The efficacy of Durvalumab compared to SoC in terms of Objective response rate (ORR) [ Time Frame: 4 years ]
  2. The efficacy of Durvalumab compared to SoC in terms of Duration of response (DoR) [ Time Frame: 4 years ]
  3. The efficacy of Durvalumab compared to SoC in terms of A Proportion of patients alive and progression free at 12 months from randomization (APF12) [ Time Frame: 12 months ]
  4. The efficacy of Durvalumab compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2) [ Time Frame: 4 years ]
  5. Disease-related symptoms and health-related quality of life in subjects treated with durvalumab compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [ Time Frame: 4 years ]
  6. The immunogenicity of durvalumab by measuring the presence of Anti-drug Antibodies [ Time Frame: 4 years ]
  7. The efficacy of Durvalumab therapy compared to SoC in terms of progress-free survival (PFS) in patients with NSCLC [ Time Frame: 4 years ]
  8. The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in PD-L1 high patients and in PD-L1 high with low risk of EM population [ Time Frame: 4 years ]
  9. Proportion of patients alive at 18 months from randomization (OS18) [ Time Frame: 18 months ]
  10. Proportion of patients alive at 24 months from randomization (OS24) [ Time Frame: 24 months ]

Other Outcome Measures:
  1. The Incidence of Treatment-Emergent Adverse Events assessed by Common Terminology Criteria for Adverse Event (CTCAE) v4.03 for subjects receiving Durvalumab therapy or SoC [ Time Frame: 4 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Aged at least 18 years
  • Documented evidence of Stage IV NSCLC
  • No sensitizing EGFR mutation and ALK rearrangement
  • PD-L1 high expression
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

  • Prior chemotherapy or any other systemic therapy for advanced NSCLC
  • Prior exposure to immune-mediated therapy, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
  • Brain metastases or spinal cord compression unless the patient is stable and off steroids for at least 14 days prior to start of study treatment
  • Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
  • Active or prior documented autoimmune or inflammatory disorders (e.g., colitis or Crohn's disease]
Contacts and Locations
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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): NCT03003962


Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Shire Norah AstraZeneca GMD IO, Gaitherburg, MD, USA
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03003962    
Other Study ID Numbers: D419AC00002
First Posted: December 28, 2016    Key Record Dates
Last Update Posted: April 1, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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 AstraZeneca:
NSCLC
PD-L1
Durvalumab (MEDI4736)
OS
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
 Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs