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

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: NCT03800134
Recruitment Status : Active, not recruiting
First Posted : January 11, 2019
Last Update Posted : May 23, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Durvalumab Other: Placebo Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Drug: Paclitaxel Drug: Gemcitabine Procedure: Surgery Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 826 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : December 6, 2018
Actual Primary Completion Date : November 10, 2022
Estimated Study Completion Date : September 11, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Arm 1: Durvalumab with platinum-based chemotherapy

Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

  • cisplatin with pemetrexed
  • carboplatin with pemetrexed
  • carboplatin with paclitaxel
  • cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
Drug: Durvalumab
1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period
Other Name: MEDI4736

Drug: Carboplatin
Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles

Drug: Cisplatin
75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles

Drug: Pemetrexed
500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Drug: Paclitaxel
200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Drug: Gemcitabine
1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Procedure: Surgery
Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.

Placebo Comparator: Arm 2: Placebo with platinum-based chemotherapy

Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity

The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:

  • cisplatin with pemetrexed
  • carboplatin with pemetrexed
  • carboplatin with paclitaxel
  • cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
Other: Placebo
Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period

Drug: Carboplatin
Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles

Drug: Cisplatin
75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles

Drug: Pemetrexed
500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Drug: Paclitaxel
200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.

Drug: Gemcitabine
1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.

Procedure: Surgery
Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.




Primary Outcome Measures :
  1. Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
    Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes.

  2. Event-Free Survival (EFS) in modified intent to treat (mITT) population [ Time Frame: Up to 5.5 years after first patient randomized. ]
    An event is defined as documented RECIST 1.1 local or distant recurrence of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery that prevents completion of surgery.


Secondary Outcome Measures :
  1. Disease-free survival (DFS) in modified resected population [ Time Frame: From date of randomization to approximately 5.5 years after date of resection ]
  2. Major Pathological Response (mPR) in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
  3. Overall Survival (OS) in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization ]
  4. Event-free survival (EFS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization ]
  5. pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
  6. Disease-Free Survival (DFS) in PD-L1-TC ≥1% patients in modified resected population [ Time Frame: From date of randomization to 5.5 years after date of resection ]
  7. Major Pathological Response (mPR) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
  8. Overall Survival (OS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization. ]
  9. To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy 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.

  10. To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy 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.

  11. To assess the PK of durvalumab in blood [ Time Frame: From date of randomization to 2 months after resection ]
    To assess concentration of durvalumab in bloodstream.

  12. 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.


Other Outcome Measures:
  1. Number of participants with adverse events as assessed by CTCAE v5.0 [ Time Frame: From date of randomization to 3 months after last dose of IP ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03800134


Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: John Heymach, MD UT MD Anderson Cancer Center
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03800134    
Other Study ID Numbers: D9106C00001
2018-002997-29 ( EudraCT Number )
First Posted: January 11, 2019    Key Record Dates
Last Update Posted: May 23, 2024
Last Verified: May 2024
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 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

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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:
Resectable Non-small Cell Lung Cancer, NSCLC, Carcinoma, Non-small Cell Lung Cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Carboplatin
Gemcitabine
Pemetrexed
Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Immunological