A Phase II Prospective Immune Neoadjuvant Therapy Study od Durvalumab (MEDI4736) in Early Stage Non-small Cell Lung Cancer

Intergroupe Francophone de Cancerologie Thoracique31 sites in 1 country50 target enrollmentJanuary 12, 2017

ConditionsCarcinoma, Non-Small-Cell Lung

InterventionsDurvalumab

DrugsDurvalumab

Overview

Phase: Phase 2
Intervention: Durvalumab
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Intergroupe Francophone de Cancerologie Thoracique
Enrollment: 50
Locations: 31
Primary Endpoint: Surgical resection R0
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Lung cancer is still the leading cause of cancer related-deaths worldwide, with an overall all-stage 5-year survival of approximately 17%. The primary treatment of early stage (I-IIIA) NSCLC is curative surgery. Although patients treated with curative surgery have a better prognosis, the 5-year survival for patients treated with surgery alone remains low, ranging from 67% (stage IA) to 23% (stage IIIA). Several randomized trials comparing postoperative chemotherapy versus no chemotherapy have shown a significant overall survival benefit from postoperative chemotherapy in completely resected patients with NSCLC stage II and IIIA. Likewise other randomized trials have demonstrated preoperative chemotherapy improves survival and recently the analyses also based on individual patients data of 15 randomized trials showed a significant benefit of preoperative chemotherapy on survival with the same survival improvement of 5% at 5 years. Then, neoadjuvant chemotherapy has also become accepted in many countries.

Targeting of PD-1 receptors and its ligand PD-L1, and inhibiting their engagement is an attractive therapeutic option in the early stage NSCLC, which may reactivate host immune responses and enable longterm tumor control.

Registry

clinicaltrials.gov

Start Date

January 12, 2017

End Date

August 28, 2019

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Intergroupe Francophone de Cancerologie Thoracique

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung.
•Tissue block of diagnosis must be available for submission after inclusion (one HES slide and one paraffin embedded block).
•Patients must be classified clinically as Stage IB (only T = 4 cm in greatest dimension, N0), Stage IIA (T2b,N0) and some of Stage IIB : (T1-2,N1) and (T3 : \> 5 cm and ≤ 7 cm in greatest dimension surrounded by lung or associated with separate tumor nodule(s) in the same lobe but without mediastinum or chest wall involvements, or superior sulcus tumors, N0) on the basis of clinical evaluation (8th classification TNM, UICC 2015). In case of invasion of the main bronchus (distance \< 2 cm from carina), a biopsy of the carina is required. A pre-surgical PET scan of the thorax and a MRI or CT scan of the brain as well as thorax abdomen pelvis CT scan must be done prior to surgery and before inclusion. If preoperative CT and/or PET are suspicious for mediastinal nodal involvement, invasive mediastinal staging with mediastinoscopy or EBUS-TBNA must be performed. Station 5 or 6 lymph nodes may be accessed by anterior mediastinotomy or VATS.
•Pre-operative (neo-adjuvant) platinum based or other chemotherapy except the treatment of the protocol is not permissible. Pre-operative radiation therapy is not permissible
•The patient must have an ECOG performance status of 0,
•Hematology (done within 14 days prior to inclusion and with values within the ranges specified below): If anemic, patients should be asymptomatic and should not be decompensated. Transfusions are permissible.
•Haemoglobin ≥ 9,0 g/dL Absolute neutrophil count \> 1.5 x 109/L or \> 1,500/µl Platelets \> 100 x 109/L or \> 100,000/µl
•Biochemistry (done within 14 days prior to inclusion and with values within the ranges specified below): 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 \> 40 ml/min TSH within normal institutional limits
•\* excluding Gilbert's syndrome
•Creatinine clearance to be measured directly by 24 hour urine sampling or as calculated by Cockcroft Formula:

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. NOTE: patients with Grave's disease and/or psoriasis not requiring systemic therapy within the last two years from inclusion are not excluded.
•History of primary immunodeficiency, history of allogenic organ transplant, use of immunosuppressive agents within 28 days of inclusion\* 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 inclusion.
•History of hypersensitivity to durvalumab 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, should have a LVEF \> 50% within 12 weeks prior to inclusion.
•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:

Arms & Interventions

Durvalumab

durvalumab 750 mg IV J1, J15, J29

Intervention: Durvalumab

Outcomes

Primary Outcomes

Surgical resection R0

Time Frame: 2 months

Patient percentage of surgical resection R0 after a maximum of 3 cycles of immune therapy

Secondary Outcomes

Delay between surgery and start of treatment(After 28 days (3 cycles of immune therapy maximum))
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(1 month)
Disease-Free Survival (DFS)(1 year)
Overall survival (OS)(1 year)
Evaluation of predictive/prognostic value of PD-1/PD-L1 expression(1 month)
Evaluation of changes in plasma/serum cytokines and other biomarkers(1 month)
Major Pathological Response(2 months)
Response Rate (recist 1.1)(After 28 days (3 cycles of immune therapy maximum))
Metabolic response rate on TEP-FDG(After 28 days (3 cycles of immune therapy maximum))