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A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer (AEGEAN)

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ClinicalTrials.gov Identifier: NCT03800134
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : January 24, 2022
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE December 7, 2018
First Posted Date  ICMJE January 11, 2019
Last Update Posted Date January 24, 2022
Actual Study Start Date  ICMJE December 6, 2018
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 26, 2021)
  • Pathological Complete Response (pCR) in modified intent-to-treat (mITT) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
    Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes.
  • Event-Free Survival (EFS) [ Time Frame: Up to 5.5 years after first patient randomized. ]
    An event defined as documented RECIST 1.1 disease progression of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery.
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2019)
Major Pathological Response (mPR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2021)
  • Disease-free survival (DFS) in modified resected population [ Time Frame: From date of randomization to 5.5 years after date of resection ]
  • Major Pathological Response (mPR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
  • Overall Survival (OS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
  • Event-free survival (EFS) in PD-L1-TC ≥1% positive patients [ Time Frame: From date of randomization to 5.5 years after randomization ]
  • pCR in PD-L1-TC ≥1% positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose ]
  • Disease-Free Survival (DFS) in PD-L1-TC ≥1% positive patients [ Time Frame: From date of randomization to 5.5 years after date of resection ]
  • Major Pathological Response (mPR) in PD-L1-TC ≥1% positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
  • Overall Survival (OS) in PD-L1-TC ≥1% positive patients [ Time Frame: From date of randomization to 5.5 years after randomization. ]
  • To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: From date of screening to 6 months after last dose of IP ]
    To assess disease-related symptoms, functioning, and global health status/quality of life in patients.
  • To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: From date of screening to 6 months after last dose of IP ]
    To assess disease-related symptoms, functioning, and global health status/quality of life in patients.
  • To assess the PK of durvalumab in blood (through concentration) [ Time Frame: From date of randomization to 2 months after resection ]
    To assess concentration of durvalumab in bloodstream.
  • Presence of ADA for durvalumab [ Time Frame: From date of randomization to 3 months after last dose of IP ]
    To evaluate the presence of antibodies following treatment with study medications.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2019)
  • Pathological complete response (pCR) [ Time Frame: From screening pathology to an average of 15 weeks after first dose. ]
  • Overall Survival (OS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
  • Event-free survival (EFS) [ Time Frame: From date of randomization to 5.5 years after randomization ]
  • Disease-free survival (DFS) [ Time Frame: From date of randomization to 5.5 years after date or resection ]
  • To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: From date of screening to 6 months after last dose of IP ]
  • To assess the PK of durvalumab in blood (through concentration) [ Time Frame: From date of randomization to 2 months after resection ]
  • Presence of ADA for durvalumab [ Time Frame: From date of randomization to 3 months after last dose of IP ]
  • mPR in PD-L1-TC positive patients [ Time Frame: From screening pathology to an average of 15 weeks after first dose ]
  • To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: From date of screening to 6 months after last dose of IP ]
Current Other Pre-specified Outcome Measures
 (submitted: May 26, 2021)
Number of participants with all adverse events as assessed by CTCAE v5.0 [ Time Frame: 64 months ]
Original Other Pre-specified Outcome Measures
 (submitted: January 8, 2019)
Number of participants with all adverse events as assessed by CTCAE v4.0 in durva + chemo prior to surgery followed by durva post-surgery compared with placebo + chemo prior to surgery followed by placebo post-surgery [ Time Frame: 82 months ]
 
Descriptive Information
Brief Title  ICMJE A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer
Official Title  ICMJE A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN).
Brief Summary This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab IV (intravenous infusion)
    Other Name: MEDI4736
  • Other: Placebo
    Placebo IV (intravenous infusion)
  • Drug: Carboplatin/Paclitaxel
    Carboplatin/Paclitaxel, as per standard of care
  • Drug: Cisplatin/Gemcitabine
    Cisplatin/Gemcitabine, as per standard of care
  • Drug: Pemetrexed/Cisplatin
    Pemetrexed/Cisplatin, as per standard of care
  • Drug: Pemetrexed/Carboplatin
    Pemetrexed/Carboplatin, as per standard of care
Study Arms  ICMJE
  • Experimental: Arm 1: Durvalumab + platinum-based chemotherapy

    Durvalumab (MEDI4736) in concurrence with platinum-based chemotherapy.

    All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on tumour histology and Investigator discretion:

    • carboplatin/paclitaxel
    • cisplatin/gemcitabine
    • pemetrexed/cisplatin
    • pemetrexed/carboplatin
    Interventions:
    • Drug: Durvalumab
    • Drug: Carboplatin/Paclitaxel
    • Drug: Cisplatin/Gemcitabine
    • Drug: Pemetrexed/Cisplatin
    • Drug: Pemetrexed/Carboplatin
  • Placebo Comparator: Arm 2: Placebo + platinum-based chemotherapy

    Placebo in concurrence with platinum-based chemotherapy.

    All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on tumour histology and Investigator discretion:

    • carboplatin/paclitaxel
    • cisplatin/gemcitabine
    • pemetrexed/cisplatin
    • pemetrexed/carboplatin
    Interventions:
    • Other: Placebo
    • Drug: Carboplatin/Paclitaxel
    • Drug: Cisplatin/Gemcitabine
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 9, 2020)
800
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2019)
300
Estimated Study Completion Date  ICMJE April 30, 2024
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥18 years
  • Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease
  • World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
  • No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
  • Adequate organ and marrow function
  • Confirmation of a patient's tumour PD-L1 status
  • Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status
  • Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy

Exclusion Criteria:

  • History of allogeneic organ transplantation
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome)
  • History of another primary malignancy
  • History of active primary immunodeficiency
  • Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus
  • Deemed unresectable NSCLC by multidisciplinary evaluation
  • Patients who have pre-operative radiotherapy treatment as part of their care plan
  • Patients who have brain metastases or spinal cord compression
  • Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
  • Known allergy or hypersensitivity to any of the study drugs or excipients
  • Existence of more than one primary tumour such as mixed small cell and NSCLC histology
  • Patients whose planned surgery at enrollment includes any of the following procedures: pneumonectomy, segmentectomies, or wedge resections
  • Patients with a documented test result confirming the presence of EGFRm or ALK translocation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator 1-877-400-4656 astrazeneca@emergingmed.com
Listed Location Countries  ICMJE Argentina,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Costa Rica,   France,   Germany,   Hungary,   India,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Peru,   Philippines,   Poland,   Puerto Rico,   Romania,   Russian Federation,   Spain,   Taiwan,   Thailand,   Ukraine,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03800134
Other Study ID Numbers  ICMJE D9106C00001
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 refer 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 deidentified 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
Principal Investigator: John Heymach, MD UT MD Anderson Cancer Institute
PRS Account AstraZeneca
Verification Date October 2021

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