Trial details

Trial short name: BR.31

Official title: A Phase III Prospective Double Blind Placebo Controlled Randomized Study of Adjuvant MEDI4736 in Completely Resected Non-Small Cell Lung Cancer

Principal Investigator: Dr. Yee Ung

Cancer type: Lung
Cancer location: Lung
Disease stage: Early and Advanced Cancer
Trial phase: Phase 3
Intervention: Drug: MEDI4736

Registration #: NCT02273375

Trial description:
The purpose of this study is to evaluate the effectiveness of the drug MEDI4736 in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who have had their tumor removed by surgery and who have not had radiation therapy may be able to participate. Patients who received chemotherapy after their surgery may be able to participate but patients cannot have received chemotherapy before their surgery. There will be two groups of patients participating in this study; one group will receive the study drug MEDI4736 while the other group will receive a placebo. The patient, doctor and study staff will not know which group a patient is in.

Inclusion Criteria: • Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung. • Patients must be classified post-operatively as Stage IB (≥ 4cm in the longest diameter), II or IIIA on the basis of pathologic criteria • 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. Resection may be accomplished by open or VATS techniques Note: Patients with synchronous primary tumours will not be eligible due to the potential uncertainty regarding their appropriate PD-L1 status. • Prior Systemic Therapy: Pre-operative (neo-adjuvant) platinum based or other chemotherapy is not permissible. • Patients may have received prior post-operative platinum based chemotherapy as per standard of care. • No prior anticancer therapy for treatment of NSCLC other than standard post operative adjuvant chemotherapy is permissible. • Radiation: Pre-operative or post-operative or planned radiation therapy is not permissible. • The patient must have an ECOG performance status of 0, 1. • Hematology: Absolute neutrophil count ≥ 1.5 x 109/L or ≥ 1,500/µl Platelets ≥ 100 x 109/L or ≥ 100,000/µl • Biochemistry: Total bilirubin* within normal institutional limits Alkaline phosphatase ≤ 2.5 x institutional upper limit of normal AST(SGOT) and ALT(SGPT) ≤ 2.5 x institutional upper limit of normal Creatinine Clearance ≥ 50 ml/min * excluding Gilbert's syndrome Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula: Females: GFR = 1.04 x (140-age) x weight in kg serum creatinine in μmol/L Males: GFR = 1.23 x (140-age) x weight in kg serum creatinine in μmol/L • Patient able and willing to complete the QoL, economics and other questionnaires. The baseline assessment must already have been completed within required timelines prior to randomization. Inability (illiteracy, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up • Protocol treatment is to begin within 2 working days of patient randomization Exclusion Criteria: • Patients with a history of other malignancies, except: adequately treated non melanoma skin cancer, curatively treated in-situ cancer, or other solid tumours 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 or pulmonary carcinoid tumour. • 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. • History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the 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. • Live attenuated vaccination administered within 30 days prior to randomization. • History of hypersensitivity to MEDI4736 or any excipient. • Mean QTc correction > 470msec in screening ECG measured standard institutional method or history of familial long QT syndrome. • 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, should have a LVEF > 50%. • 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 prior history of tuberculosis; - known acute hepatitis B or C by serological evaluation; - known Human immunodeficiency virus infection. • Pregnant or lactating women. Women of childbearing potential must have a urine pregnancy test proven negative within 14 days prior to randomization. Men and women of child-bearing potential must agree to use adequate contraception.