non-small cell lung cancer stages IIIA (N2) and selected resectable stages IIIB MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: IMFINZI®
Product Name: Durvalumab
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DURVALUMAB
Other descriptive name: MEDI4736
Concent
Sponsors
University Hospital Essen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Body weight >30 kg 2. Age = 18 years and = 75 years 3. Male or female patients. Female (as well as male) patients have to take care of effective measures of anticonception 4. Histologically proven non-small cell lung cancer 5. Selected patients with non-small cell lung cancer stages IIIA and IIIB: • IIIA: one or more lymph node levels involved at EBUS/mediastinoscopy • IIIA: bulky N2-disease histologically proven at EBUS/cervical mediastinoscopy / parasternal mediastinotomy, not diffuse mediastinal involvement • selected IIIB: N3-disease with contralateral mediastinal nodes involved at EBUS / mediastinoscopy • potentially resectable T4-disease: o involvement of the pulmonary artery (angiogr.-CT/MRI/TEE), o involvement of the carina (histologically proven), o involvement of the left atrium (angiogr.-CT/MRI/TEE), o involvement of the vena cava (angiogr.-CT/MRI/TEE), o involvement of ipsilateral intrapulmonary satellite nodules, o mediastinal involvement (not diffuse) 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 7. Resectable disease at the time of inclusion 8. Fulfillment of adequate criteria for functional and medical resectability as described in the ERS/ESTS guidelines [Brunelli et al 2009] and acceptable general clinical condition for multimodality treatment (interdisciplinary committee) 9. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations 10. Must have a life expectancy of > 12 weeks 11. Adequate normal organ and marrow function as defined below: o Haemoglobin = 9.0 g/dL o Absolute neutrophil count (ANC) > 1.5 x 109/L (> 1500 per mm3) o Platelet count = 100 x 109/L (= 100.000 per mm3) o Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. o AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal o Measured creatinine clearance (CL) > 40 mL/min or Calculated creatinine CL > 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance 12. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up 14. Stable cardiac function (no Myocardial infarction (MI) within 6 months, no heart failure NYHA III-IV) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. resectable IIB or selected IIIA 2. unresectable disease pre-treatment 3. mixed histology with areas of small cell carcinoma 4. clinically symptomatic vena cava superior syndrome 5. diffuse mediastinal involvement 6. patients with T3N3 and T4N3 tumors 7. invasion of the thoracic aorta 8. invasion of the heart 9. invasion of the esophagus 10. invasion of spine 11. Pancoast-syndrome in tumors of the superior sulcus 12. malignant pericardial effusion 13. malignant pleural effusion 14. involvement of the contralateral hilar nodes 15. endobronchial tumor extension to the contralateral main stem bronchus 16. ipsi- or contralateral supraclavicular nodes 17. lung or heart function not allowing at the time of inclusion the intended surgical procedure 18. previous administration of chemotherapy and/or radiotherapy within five years prior to randomization 19. previous immunotherapy within five years prior to randomization 20. insufficient patients compliance 21. loss of weight > 10 % in the last six months 22. missing written informed consent or definitive refusal for participation 23. Participation in another clinical study with an investigational product during the last 12 months 24. Concurrent enrolment in another clinical study, unless it is an observational clinical study or during the follow-up period of an interventional study 25. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day 26. History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan 27. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable 28. Major surgical procedure within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable 29. History of allogenic organ transplantation 30. History of a stem cell transplantation 31. 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.]). 32. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled diabetes, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 33. History of another primary malignancy 34. History of active primary immunodeficiency 35. Active infection including tuberculosis hepatitis B, hepatitis C, or human immunodeficiency virus. Patients with a past or resolved HBV infection are eligible. Patients positive for hepatitis C antibody are eligible only if polymerase chain reaction is negative for HCV RNA 36. Current or prior use of immunosuppres
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the efficacy of a multimodality treatment in resectable stage III non-small-cell lung cancer patients including a complex induction chemoimmunotherapy followed by a radiochemoimmunotherapy and definitive surgical resection or radiochemotherapy-boost and immunotherapy consolidation for 32 weeks versus the same multimodality treatment protocol without immunotherapy in the induction and radiochemotherapy as measured by two-year progression-free survival.;Secondary Objective: The secondary objective is to analyze the toxicity and efficacy of a multimodality treatment in resectable stage III non-small-cell lung cancer patients including a complex induction chemoimmunotherapy followed by a radiochemoimmunotherapy and definitive surgical resection or radiochemotherapy-boost and immunotherapy consolidation for 32 weeks versus the same multimodality treatment protocol without immunotherapy in the induction and radiochemotherapy as measured by response, survival parameters, QoL, compliance and treatment toxicity effects. The secondary objective will be will be achieved by the following secondary endpoints: • To investigate the rate of pathological complete response • To investigate the toxicity and the following surgical resection • To investigate 2-y-overall survival rate • To investigate functional and RECIST response • Progression free survival time • Overall survival • Histopathologic complete response • Other adverse events • Quality of life;Primary end point(s): The primary endpoint is the progression-free survival rate ;Timepoint(s) of evaluation of this end point: The primary endpoint will be analyzed after the end of 2 year follow-up of the last treated patient. The observed proportion will be compared with the expected proportion of 35% using the exact binominal test. If the observed proportion is significantly larger than 0.35 using a one sided exact binominal test at alpha=0.025, than the gate is opened for a se | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival - Occurrence of pulmonary adverse effects of grade > 3 according to CTCAE 5.0. - Occurrence of immune therapy related adverse effects of grade > 3 according to CTCAE v.5.0. - Adverse events with at least probable relationship to study procedures will counted in total and separate according to CTCAE criteria. - Quality of life (QoL C30 and Qol-LC13) date will be analyzed descriptively calculation mean scores, standard deviations median minimum and maximum of the scores. See also section 11.4.5.2. ;Timepoint(s) of evaluation of this end point: - Overall survival: Median survival time and survival rates after 1, 2, 3, and 4 years will be estimated together with 95% confidence limits. - All other secondary endpoints will be analyzed after the end of 2 year follow-up of the last treated patient. | — |
Countries
Germany
Contacts
Public ContactStudy Coordination
Universitätsmedizin Essen - Studienzentrum GmbH
Outcome results
None listed