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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 : July 7, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE December 15, 2016
First Posted Date  ICMJE December 28, 2016
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE January 2, 2017
Estimated Primary Completion Date January 25, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
  • The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in all randomized patients [ Time Frame: 4 years ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2016)
  • The efficacy of Durvalumab therapy compared to SoC in terms of progression-free survival (PFS) in patients with NSCLC [ Time Frame: 3 years ]
  • The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in patients with NSCLC [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
  • The efficacy of Durvalumab compared to SoC in terms of Objective response rate (ORR) [ Time Frame: 4 years ]
  • The efficacy of Durvalumab compared to SoC in terms of Duration of response (DoR) [ Time Frame: 4 years ]
  • 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 ]
  • The efficacy of Durvalumab compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2) [ Time Frame: 4 years ]
  • 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 ]
  • The immunogenicity of durvalumab by measuring the presence of Anti-drug Antibodies [ Time Frame: 4 years ]
  • The efficacy of Durvalumab therapy compared to SoC in terms of progress-free survival (PFS) in patients with NSCLC [ Time Frame: 4 years ]
  • 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 ]
  • Proportion of patients alive at 18 months from randomization (OS18) [ Time Frame: 18 months ]
  • Proportion of patients alive at 24 months from randomization (OS24) [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2016)
  • The efficacy of Durvalumab compared to SoC in terms of Objective response rate (ORR) [ Time Frame: 3 years ]
  • The efficacy of Durvalumab compared to SoC in terms of Duration of response (DoR) [ Time Frame: 3 years ]
  • 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 ]
  • The efficacy of Durvalumab compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2) [ Time Frame: 3 years ]
  • Disease-related symptoms in subjects treated with durvalumab compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-LC13) [ Time Frame: 3 years ]
  • 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 (EORTC QLQ-C30) [ Time Frame: 3 years ]
  • The immunogenicity of durvalumab by measuring the presence of Anti-drug Antibodies [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures
 (submitted: June 1, 2018)
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 ]
Original Other Pre-specified Outcome Measures
 (submitted: December 22, 2016)
The Incidence of Treatment-Emergent Adverse Events assessed by CTCAE v4.03 for subjects receiving Durvalumab therapy or SoC [ Time Frame: 3 years ]
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)
Official Title  ICMJE 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
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)
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Carcinoma NSCLC
Intervention  ICMJE
  • Drug: Durvalumab (MEDI4736)
    Anti-PD-L1 monoclonal Antibody monotherapy
  • 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
Study Arms  ICMJE
  • Experimental: Arm 1: Durvalumab
    Anti-PD-L1 monoclonal Antibody monotherapy
    Intervention: Drug: Durvalumab (MEDI4736)
  • Active Comparator: Arm 2: Standard of Care
    Standard of Care Platinum-Based chemotherapy
    Interventions:
    • Drug: Paclitaxel + carboplatin
    • Drug: Gemcitabine + cisplatin
    • Drug: Gemcitabine + carboplatin
    • Drug: Pemetrexed + cisplatin
    • Drug: Pemetrexed + carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 16, 2019)
669
Original Estimated Enrollment  ICMJE
 (submitted: December 22, 2016)
440
Estimated Study Completion Date  ICMJE January 25, 2021
Estimated Primary Completion Date January 25, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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]
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   China,   Hungary,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Taiwan,   Thailand,   Turkey,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03003962
Other Study ID Numbers  ICMJE D419AC00002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Shire Norah AstraZeneca GMD IO, Gaitherburg, MD, USA
PRS Account AstraZeneca
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP