None listed
Conditions
Brief summary
BR.31 a clinical research study that is testing MEDI4736, a new type of drug for the treatment of non-small cell lung cancer (NSCLC) that was completely removed with surgery. It is being led by the Australasian Lung Cancer Trials Group (ALTG) and coordinated by the National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC). The purpose of this study is to find out whether it is better to receive the new drug, MEDI4736, or no further treatment after surgery (and possibly chemotherapy) for lung cancer. The study involves randomly allocating participants to receive treatment with either MEDI4736 or placebo, a substance that has no active medicine in it. Two-thirds (2/3) of the participants in this study will receive MEDI4736 and the other third (1/3) will receive placebo. Participants will be required to receive intravenous infusions of MEDI4736 or placebo at 20mg/kg every 4 weeks for 12 months. Participants will then be followed up for a maximum of 10 years to assess overall survival and disease free survival.
Interventions
MEDI4736 by intravenous infusion. MEDI4736 is supplied as a vialed liquid solution containing 500mg (nominal) MEDI4736. The solution contains 50mg/mL MEDI4736, 26mM histidine/histidine-HCl, 275mM trehalose dehydrate, 0.02% (w/v) polysorbate 80, at pH 6.0.
Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.
Dosages are as follows: 20mg/kg every 4 weeks for 12 months.
Sponsors
NHMRC Clinical Trials Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung *Patients must be classified post-operatively as Stage IB (greater than or equal to 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 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 radiation therapy is not permissible. *Patients with N2 disease only who receive adjuvant post-operative radiation therapy are eligible provided they meet the protocol specified timing criteria for surgery, adjuvant chemotherapy and randomization. *The patient must have an ECOG performance status of 0, 1. *Hematology: . Absolute neutrophil count greater than or equal to 1.5 x 109/L or greater than or equal to 1,500/microlitres Platelets greater than or equal to 100 x 109/L or greater than or equal to 100,000/microlitres *Biochemistry: Total bilirubin* within normal institutional limits Alkaline phosphatase less than or equal to 2.5 x institutional upper limit of normal AST(SGOT) and ALT(SGPT) less than or equal to 2.5 x institutional upper limit of normal Creatinine Clearance greater than or equal to 50 ml/min * excluding Gilbert's syndrome Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula: For females, GFR is equivalent to [1.04 x (140-age) x weight in kg] / serum creatinine in micromol/L For males, GFR is equivalent to [1.23 x (140-age) x weight in kg] / serum creatinine in micromol/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 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 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. Men and women of child-bearing potential must agree to use adequate contraception
Outcome results
None listed