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)
- Conditions
- -C349 Bronchus or lung, unspecifiedBronchus or lung, unspecifiedC349
- Registration Number
- PER-017-20
- Lead Sponsor
- AstraZeneca AB,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Not specified
- Target Recruitment
- 0
Informed consent
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
2. Provision of signed and dated written ICF prior to any mandatory study specific procedures, sampling, and analyses
3. Provision of signed and dated written ICF prior to collection of sample for genetic analysis
Age
4. Age ≥18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
Type of patient and disease characteristics
5. Histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease (according to Version 8 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology 2016]).
− At screening, complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multidisciplinary evaluation, which must include a thoracic surgeon who performs lung cancer surgery as a prominent part of his/her practice.
− Nodal status should be investigated with whole body 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET), plus contrast-enhanced computed tomography (CT). If PET/CT scan is positive in the mediastinum, or if scan is negative but there is T>3 cm, central tumor, or clinical N1 (cN1), then it is recommended that nodal status be proven by biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. See Section 6.1.3 (preoperative mediastinal lymph node staging) for more details.
− Mandatory brain magnetic resonance imaging (MRI; preferred) with IV contrast or brain CT with IV contrast at the time of staging.
6. World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
7. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by CT or MRI scan must be performed within 28 days prior to randomization.
8. 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.
9. Adequate organ and marrow function as defined below:
− Hemoglobin ≥9.0 g/dL
− Absolute neutrophil count ≥1.5 × 109/L
− Platelet count ≥100 × 109/L
− Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
− ALT and AST ≤2.5 × ULN
− Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min as determined by Cockcroft-Gault (using actual body WT)
10. Must have a life expectancy of at least 12 weeks
Weight
11. Body WT >30 kg
Sex
12. Male and/or female
Tumor sample requirements:
13. Confirmation of a patient’s tumor PD-L1 status must occur prior to randomization using Ventana PD-L1 (SP263) immunohistochemistry (IHC) assay applied to formalin fixed paraffin embedded tissue sample with testing completed by the central laboratory. Samples for PD-L1 testing may include the following:
− Newly acquired tumor tissue (preferred) or
Medical conditions
1 History of allogeneic organ transplantation
2 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [eg, granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, or uveitis]). The following are exceptions to this criterion:
− Patients with vitiligo or alopecia
− Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
− Any chronic skin condition that does not require systemic therapy
− Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
− Patients with celiac disease controlled by diet alone
3 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent
4 History of another primary malignancy, except for the following:
− Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
− Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
− Adequately treated carcinoma in situ without evidence of disease
5 History of active primary immunodeficiency
6 Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
7 Deemed unresectable NSCLC by multidisciplinary evaluation that must include a thoracic surgeon who perform lung cancer surgery as a significant part of their practice
8 Patients who have pre-operative radiotherapy treatment as part of their care plan
9 Patients who have brain metastases or spinal cord compression. All patients will have an MRI (preferred) or high-quality CT with IV contrast of the brain, prior to study entry.
10 Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
11 Mean QT interval corrected for heart rate using Fridericia´s formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
12 Mixed small cell and NSCLC histology
13 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
14 Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Investigator assessment using RECIST1.1<br>Measure:Event-free survival (EFS)<br>Timepoints:From randomization until disease progression or death<br>;<br>Outcome name:10% or less residual viable tumor tissue in lung primary tumor after neoadjuvant treatment at the time of resection<br>Measure:Major pathological response (mPR)<br>Timepoints:Since begining of neoadjuvant treatment, until surgery<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Efficacy of durvalumab + chemotherapy administered prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy administered prior to surgery, followed by placebo post-surgery in terms of DFS<br>Measure:Disease Free survival (DFS)<br>Timepoints:Since randomization until disease progression or death<br>;<br>Outcome name:Absence of any residual viable tumor in the primary lung lesion and lymph nodes at the time of surgical resection<br>Measure:Pathological complete response (pCR)<br>Timepoints:Since neoadjuvant therapy until surgery<br>;<br>Outcome name:Efficacy of durvalumab + chemotherapy administered prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy administered prior to surgery followed by placebo post-surgery in terms of OS<br>Measure:Overall survival<br>Timepoints:Since randomization until death<br>