Comparison of two treatment arms of patients with non-small cell lung cancer. Patients of one arm receive the authorized infusion Durvalumab after chemotherapy, chemotherapy with radiotherapy and optional resection. Patients in the second treatment arm receive Durvalumab from the beginning, in parallel with standard therapy.
- Conditions
- non-small cell lung cancer stages IIIA (N2) and selected resectable stages IIIBMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000058-77-DE
- Lead Sponsor
- niversity Hospital Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method