Study in Patients with surgically removable Non-Small Cell Lung Cancer (NSCLC) with Durvalumab plus Chemotherapy before and after surgical removal of tumour versus surgical removal of tumour alone with chemotherapy
- Conditions
- Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
- Registration Number
- CTRI/2019/06/019634
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- 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).
i).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.
ii).Nodal status should be investigated with whole body 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET), plus contrast-enhanced computed tomography (CT) in addition to or in combination with PET before surgery. 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 nodal status should be proven by biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy. (preoperative mediastinal lymph node staging).
iii).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 enrolment.
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:
i).Hemoglobin =9.0 g/dL
ii).Absolute neutrophil count =1.5 × 109/L
iii).Platelet count =100 × 109/L
iv).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.
v).ALT and AST =2.5 × ULN
vi).Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min as determined by Cockcroft-Gault (using actual body WT)
Males:
Creatinine CL is equal to WT (kg) × (140-Age) (mL/min) 72 × serum creatinine (mg/dL)
Females:
Creatinine CL is equal to WT (kg) × (140-Age) × 0.85(mL/min) 72 × serum creatinine (mg/dL)
10. Must have a life expectancy of at least 12 weeks.
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
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:
i).Patients with vitiligo or alopecia.
ii).Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on
iii).hormone replacement.
iv).Any chronic skin condition that does not require systemic therapy.
v).Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician
vi).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:
i).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
ii).Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
iii).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 Fridericias 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 stud
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare the efficacy of durvalumab +chemotherapy administered prior to surgery followed <br/ ><br>by durvalumab post-surgery compared with placebo+ chemotherapy administered prior to surgery <br/ ><br>followed by placebo post-surgery in terms of EFS <br/ ><br>To assess the activity of durvalumab + chemotherapy administered prior to surgery compared with placebo+ chemotherapy administered prior to surgery in terms of mPRTimepoint: EFS <br/ ><br> <br/ ><br>mPR (10% or less residual viable tumor tissue in lung primary tumor after neoadjuvant treatment at the time of resection)
- Secondary Outcome Measures
Name Time Method