lung cancer Non-small cell lung carcinoma
Conditions
Interventions
Patients will receive two courses of durvalumab (MEDI4736)at a fixed dose of
750mg Q2W intravenously, prior to scheduled resection of NSCLC. Patients are
amendable to adjuvant chemo and/or radiation
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: All patients must meet all of the following criteria:;1. Male or female subjects aged >50 years at time of study entry 2. Histopathological proven primary non-small cell lung cancer, with fully evaluable histological biopsies available 3. ECOG performance status of 0 or 1 4. AJCC stage I, II or IIIa as determined by contrast-enhanced CT chest-abdomen and F-18-FDG PET/CT: cT1cN0-1M0, cT2aN0-1M0 en cT3N0-1M0 (T3 separate nodule) 5. Solid appearance of the tumor on contrast-enhanced CT 6. Scheduled for resection with curative intent 7. Patients should be medically operable defined by: 8. Sufficient cardiopulmonary function 9. Major contra-indications for surgery. 10. No underlying immune disease (neutro- or lymphopenia, coagulation disorders) that could interfere with T-cell isolation 11. Life expectancy at least 6 months 12. Written informed consent and comply with study protocol for the duration of the study and follow-up 13. Adequate laboratory values (refer to study protocol)
Exclusion criteria
Exclusion criteria: A patient will be excluded from participation in the trial if one or more of the following criteria are met:;1. Inability to lie supine for more than 30 minutes 2. Documented previous severe allergic reaction to iodine-based contrast media, despite adequate pre-medication. 3. Indication for cervical mediastinoscopy 4. Participation in another clinical study with an investigational product during the past 6 months 5. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 6. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) <6 months prior to the first dose of study drug 7. Any unresolved toxicity NCI CTCAE Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 8. Patients with Grade >=2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 9. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab (MEDI4736) may be included only after consultation with the Study Physician. 10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 11. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 6 months of the first dose of study drug 12. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. 13. History of allogenic organ transplantation. 14. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). 15. History of another primary malignancy except for: 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, Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, Adequately treated carcinoma in situ without evidence of disease 16. History of active primary immunodeficiency 17. Active infection including: tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, human immunodeficiency virus (positive HIV 1/2 antibodies), Epstein Barr Virus (EBV, positive IgM antibodies), cytomegalo virus (CMV, positive IgM antibodies) 18. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (MEDI4736); exceptions apply. 19. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab (MEDI4736). Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab (MEDI4736) and up to 30 days after the last dose of durvalumab (MEDI4736). 20. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not wil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| he primary endpoint of this study will be to demonstrate 1) feasibility and 2) safety of two courses durvalumab (MEDI4736) 750 mg Q2W in neo-adjuvant setting in resectable NSCLC. Study parameter 1): no delayed surgical procedures, all surgery should be performed within 42 days after the first therapeutic dose of durvalumab (MEDI4736). Study parameter 2): number of grade 3 or higher adverse events related to durvalumab (MEDI4736). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Correlative studies across different imaging modalities. 2. Validation of in vivo imaging findings with other potential biomarkers derived from quantitative immune histochemistry and peripheral blood immune profiling. 3. Assessment of neo-adjuvant durvalumab (MEDI4736) on outcome measures related to clinical care. | — |
Countries
Netherlands
Outcome results
None listed