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 |
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Recruitment Status :
Active, not recruiting
First Posted : January 11, 2019
Last Update Posted : February 29, 2024
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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 |
| 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 Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
Drug Information
available for:
Durvalumab
| Arm | Intervention/treatment |
|---|---|
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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:
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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 IP following the completion of neoadjuvant treatment (4 cycles of platinum based chemotherapy concurrent with durvalumab or placebo) |
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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:
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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 IP following the completion of neoadjuvant treatment (4 cycles of platinum based chemotherapy concurrent with durvalumab or placebo) |
Primary Outcome Measures :
- 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.
- 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 :
- Disease-free survival (DFS) in modified resected population [ Time Frame: From date of randomization to approximately 5.5 years after date of resection ]
- Major Pathological Response (mPR) in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
- Overall Survival (OS) in modified intent to treat (mITT) population [ Time Frame: From date of randomization to 5.5 years after randomization ]
- 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 ]
- pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population [ Time Frame: Up to approximately 15 weeks after randomization ]
- 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 ]
- 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 ]
- 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. ]
- 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.
- 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.
- 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.
- 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:
- 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 ]
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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
Show 231 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | John Heymach, MD | UT MD Anderson Cancer Center |
| 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: | February 29, 2024 |
| Last Verified: | February 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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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 |