Malignant neoplasm of bronchus or lung, unspecified
Conditions
Interventions
Safety and efficacy clinical of MEDI4736. It will be included 1360 patients, any gender, aging 18 years or older in 19 countries in the world. As control, placebo will be used. Control group: 453 pati
Drug
Sponsors
Canadian Cancer Trials Group
Clinipace Pesquisas Clínicas do Brasil Ltda. - CPWW
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung (NSCLC) according to WHO Classification of Tumours. Patients with large-cell neuroendocrine carcinomas are not eligible. Patients must consent to release of an adequate histological specimen for this protocol, and the tissue blocks must be available for submission after registration. Failure to provide tissue blocks for PD-L1 expression assessment will render the patient ineligible; patients must be classified post-operatively as Stage IB (> 4cm in the longest diameter), II or IIIA based on pathologic criteria; surgery and previous therapy for NSCLC: a pre-surgical PET scan of the thorax and a MRI or CT scan of the brain is considered standard of care and thus must be done prior to surgery. Patients in whom this was not done prior to surgery may still be enrolled providing that appropriate imaging is performed prior to randomization; b. complete surgical resection of the primary NSCLC is also mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for tumour; c. lymph node mapping is defined by The International Association for the Study of Lung Cancer (IASLC) lymph node map. The nodal tissue should be labelled according to the recommendations of the American Thoracic Society. Accordingly, it is recommended that a minimum of 3 (three) lobe specific mediastinal nodal stations (N2), one of which should include station 7, and at least one N1 station - inclusive of the ones removed with the pulmonary specimen have been sampled at the end of the procedure; d. if preoperative CT and/or PET are suspicious for mediastinal nodal involvement, it is recommended that invasive mediastinal staging with mediastinoscopy or EBUS-TBNA be performed. Station 5 or 6 lymph nodes may be accessed by anterior mediastinotomy or VATS. This may also occur at the time of the surgical resection. If invasive staging shows disease in regional lymph nodes, they must be surgically removed. It is recommended that complete mediastinal lymph node dissection be undertaken for stage IIIA tumours; e. surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the intraoperative findings. Patients who have had only segmentectomies or wedge resections are not eligible for this study. Note: Where a resection has been extended by means of a wedge resection of an adjacent lobe in order to ensure complete resection of a tumour at or crossing a fissure between lobes, if the margins are clear this is acceptable. Where the resection of a second tumour nodule, even where not considered to be a co-primary, is undertaken by means of a wedge resection of a separate lobe then the patient is not eligible; prior systemic therapy: a. pre-operative (neo-adjuvant) platinum based or other chemotherapy is not permissible; b. patients may have received prior post-operative platinum based chemotherapy as per standard of care. Patients who discontinue chemotherapy for toxicity prior to completion of all planned chemotherapy are eligible; c. if adjuvant platinum-based chemotherapy is given, it is strongly recommended that this be started within 8 weeks of surgery; d. patients must have recovered from all acute, reversible toxic effects from chemotherapy (excluding alopecia); e. patients who have not received adjuvant chemotherapy, and meet all other eligibility criteria, may be elig
Exclusion criteria
Exclusion criteria: Patients with a history of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated with no evidence of disease for > 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy; a combination of small cell and non-small cell lung cancer, pulmonary carcinoid tumour or large-cell neuroendocrine carcinoma (LCNEC); history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Note: patients with Grave’s disease and/or psoriasis not requiring systemic therapy within the last two years from randomization and patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement are not excluded; history of primary immunodeficiency, history of allogenic organ transplant, use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy (* note: intranasal/inhaled corticosteroids or systemic steroids that do not to exceed 10 mg/day of prednisone or equivalent dose of an alternative corticosteroid are permissible); live attenuated vaccination administered within 30 days prior to randomization; history of hypersensitivity to MEDI4736 or any excipient; patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, must have a LVEF > 50% within 12 weeks prior to randomization; concurrent treatment with other investigational drugs or anti-cancer therapy; patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol [this includes but is not limited to: known clinical diagnosis of tuberculosis; known active hepatitis B infection (positive HBV surface antigen (HBsAg)). Patients with a past or resolved hepatitis B infection (defined as presence of hepatitis B core antibody (anti-HBc) and absence of HBSAg) are eligible; known active hepatitis C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RA; known human immunodeficiency virus infection (positive HIV antibodies); known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function]; pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 14 days prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the disease free survival which is defined as the time from the date of randomization to the date of first documented disease relapse or the occurrence of a new invasive primary malignancy or death from any cause. Patients who are alive and disease or new invasive primary malignancy-free at the time of each analysis will be censored at their last disease assessment date | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the overall survival which is defined as the time from the randomization to the date of death of any cause, or censored at their last known alive date;To evaluate the lung cancer specific survival which is defined as the time from the date of randomization to the date of patients died of lung cancer, or censored at the last contact date | — |
Countries
Australia, Brazil, Bulgaria, Canada, China, France, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, Republic of Korea, Romania, Singapore, Spain, Taiwan, Ukraine, United States
Contacts
Public ContactHelena Petridis
Clinipace Pesquisas Clínicas do Brasil Ltda. - CPWW
Outcome results
None listed