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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03003962




Registration number
NCT03003962
Ethics application status
Date submitted
15/12/2016
Date registered
28/12/2016

Titles & IDs
Public title
Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)
Scientific 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
Secondary ID [1] 0 0
2018-001375-21
Secondary ID [2] 0 0
D419AC00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Carcinoma NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab (MEDI4736)
Treatment: Drugs - Paclitaxel + carboplatin
Treatment: Drugs - Gemcitabine + cisplatin
Treatment: Drugs - Gemcitabine + carboplatin
Treatment: Drugs - Pemetrexed + cisplatin
Treatment: Drugs - Pemetrexed + carboplatin

Experimental: Arm 1: Durvalumab - Anti-PD-L1 monoclonal Antibody monotherapy

Active comparator: Arm 2: Standard of Care - Standard of Care Platinum-Based chemotherapy


Treatment: Drugs: Durvalumab (MEDI4736)
Anti-PD-L1 monoclonal Antibody monotherapy

Treatment: Drugs: Paclitaxel + carboplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + cisplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + carboplatin
Chemotherapy Agents

Treatment: Drugs: Pemetrexed + cisplatin
Chemotherapy Agent

Treatment: Drugs: Pemetrexed + carboplatin
Chemotherapy Agent

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

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]
Primary outcome [2] 0 0
OS in Participants With LREM
Timepoint [2] 0 0
From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [1] 0 0
OS in PD-L1 TC >= 50% Analysis Set
Timepoint [1] 0 0
From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [2] 0 0
OS in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [2] 0 0
From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [3] 0 0
Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [3] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months DCO 27 October 2022)
Secondary outcome [4] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set
Timepoint [4] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [5] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set
Timepoint [5] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [6] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [6] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [7] 0 0
Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment
Timepoint [7] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [8] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [8] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [9] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set
Timepoint [9] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [10] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [10] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [11] 0 0
Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment
Timepoint [11] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [12] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set
Timepoint [12] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [13] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set
Timepoint [13] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [14] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set
Timepoint [14] 0 0
Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)
Secondary outcome [15] 0 0
Alive and Progression-Free at 12 Months (APF12)
Timepoint [15] 0 0
From date of randomization until 12 months
Secondary outcome [16] 0 0
APF12 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [16] 0 0
From date of randomization until 12 months
Secondary outcome [17] 0 0
APF12 in PD-L1 TC >= 50% Analysis Set
Timepoint [17] 0 0
From date of randomization until 12 months
Secondary outcome [18] 0 0
APF12 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [18] 0 0
From date of randomization until 12 months
Secondary outcome [19] 0 0
Time From Randomization to Second Progression (PFS2)
Timepoint [19] 0 0
Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)
Secondary outcome [20] 0 0
PFS2 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [20] 0 0
Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)
Secondary outcome [21] 0 0
PFS2 in PD-L1 TC >= 50% Analysis Set
Timepoint [21] 0 0
Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)
Secondary outcome [22] 0 0
PFS2 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [22] 0 0
Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)
Secondary outcome [23] 0 0
OS at 18 Months
Timepoint [23] 0 0
From date of randomization till 18 months.
Secondary outcome [24] 0 0
OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set
Timepoint [24] 0 0
From date of randomization till 18 months
Secondary outcome [25] 0 0
OS at 18 Months in PD-L1 TC >= 50% Analysis Set
Timepoint [25] 0 0
From date of randomization till 18 months
Secondary outcome [26] 0 0
OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [26] 0 0
From date of randomization till 18 months
Secondary outcome [27] 0 0
OS at 24 Months
Timepoint [27] 0 0
From date of randomization till 24 months
Secondary outcome [28] 0 0
OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set
Timepoint [28] 0 0
From date of randomization till 24 months
Secondary outcome [29] 0 0
OS at 24 Months in PD-L1 TC >= 50% Analysis Set
Timepoint [29] 0 0
From date of randomization till 24 months
Secondary outcome [30] 0 0
OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [30] 0 0
From date of randomization till 24 months
Secondary outcome [31] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)
Timepoint [31] 0 0
Baseline and 12 months
Secondary outcome [32] 0 0
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [32] 0 0
Baseline and 12 months
Secondary outcome [33] 0 0
Time to Deterioration of EORTC QLQ-C30
Timepoint [33] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [34] 0 0
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [34] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [35] 0 0
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)
Timepoint [35] 0 0
Baseline and 12 months
Secondary outcome [36] 0 0
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [36] 0 0
Baseline and 12 months
Secondary outcome [37] 0 0
Time to Deterioration of EORTC QLQ-LC13
Timepoint [37] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [38] 0 0
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [38] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [39] 0 0
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [39] 0 0
From Baseline and until follow-up period of 57 months
Secondary outcome [40] 0 0
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set
Timepoint [40] 0 0
From Baseline and until follow-up period of 57 months
Secondary outcome [41] 0 0
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab
Timepoint [41] 0 0
Up to 24 weeks
Secondary outcome [42] 0 0
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set
Timepoint [42] 0 0
Up to 24 weeks

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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]

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
Open (masking not used)
Who is / are masked / blinded?



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)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Gosford
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
China
State/province [2] 0 0
Beijing
Country [3] 0 0
China
State/province [3] 0 0
Bengbu
Country [4] 0 0
China
State/province [4] 0 0
Changchun
Country [5] 0 0
China
State/province [5] 0 0
Changsha
Country [6] 0 0
China
State/province [6] 0 0
Chengdu
Country [7] 0 0
China
State/province [7] 0 0
Chongqing
Country [8] 0 0
China
State/province [8] 0 0
Guangzhou
Country [9] 0 0
China
State/province [9] 0 0
Haikou
Country [10] 0 0
China
State/province [10] 0 0
Hangzhou
Country [11] 0 0
China
State/province [11] 0 0
Jinan
Country [12] 0 0
China
State/province [12] 0 0
Linhai
Country [13] 0 0
China
State/province [13] 0 0
Nanchang
Country [14] 0 0
China
State/province [14] 0 0
Nanjing
Country [15] 0 0
China
State/province [15] 0 0
Ningbo
Country [16] 0 0
China
State/province [16] 0 0
Shanghai
Country [17] 0 0
China
State/province [17] 0 0
Shenyang
Country [18] 0 0
China
State/province [18] 0 0
Shijiazhuang
Country [19] 0 0
China
State/province [19] 0 0
Urumqi
Country [20] 0 0
China
State/province [20] 0 0
Wanzhou
Country [21] 0 0
China
State/province [21] 0 0
Wenzhou
Country [22] 0 0
China
State/province [22] 0 0
Wuhan
Country [23] 0 0
China
State/province [23] 0 0
Xi'an
Country [24] 0 0
China
State/province [24] 0 0
Zhengzhou
Country [25] 0 0
China
State/province [25] 0 0
Zhuhai
Country [26] 0 0
Hungary
State/province [26] 0 0
Budapest
Country [27] 0 0
Hungary
State/province [27] 0 0
Deszk
Country [28] 0 0
Hungary
State/province [28] 0 0
Farkasgyepü
Country [29] 0 0
Hungary
State/province [29] 0 0
Gyöngyös - Mátraháza
Country [30] 0 0
Hungary
State/province [30] 0 0
Székesfehérvár
Country [31] 0 0
Hungary
State/province [31] 0 0
Törökbálint
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Changwon-si
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Cheongju-si
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Daegu
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Incheon
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Jinju-si
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Suwon-si
Country [39] 0 0
Netherlands
State/province [39] 0 0
Almelo
Country [40] 0 0
Poland
State/province [40] 0 0
Bialystok
Country [41] 0 0
Poland
State/province [41] 0 0
Grudziadz
Country [42] 0 0
Poland
State/province [42] 0 0
Koszalin
Country [43] 0 0
Poland
State/province [43] 0 0
Lublin
Country [44] 0 0
Poland
State/province [44] 0 0
Mrozy
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Poland
State/province [46] 0 0
Wroclaw
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Arkhangelsk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Novosibirsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Omsk
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Rostov-on-Don
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Saint Petersburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Saint-Petersburg
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Sankt-Peterburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
St. Petersburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Volgograd
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taichung City
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
Thailand
State/province [60] 0 0
Bangkok
Country [61] 0 0
Thailand
State/province [61] 0 0
Muang
Country [62] 0 0
Thailand
State/province [62] 0 0
Songkla
Country [63] 0 0
Turkey
State/province [63] 0 0
Ankara
Country [64] 0 0
Turkey
State/province [64] 0 0
Istanbul
Country [65] 0 0
Turkey
State/province [65] 0 0
Malatya
Country [66] 0 0
Turkey
State/province [66] 0 0
Pamukkale
Country [67] 0 0
Vietnam
State/province [67] 0 0
Can Tho
Country [68] 0 0
Vietnam
State/province [68] 0 0
Hanoi
Country [69] 0 0
Vietnam
State/province [69] 0 0
Ho Chi Minh

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Address 0 0
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 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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.