ESPADURVA

Studieninformationen

Studien-Code

UME-ID-8773

Studien-Akronym

ESPADURVA

Studientitel

Prospective Phase-II Trial of induction chemotherapy and chemoradiotherapy plus/minus the PD-L1 antibody durvalumab followed by surgery or definitive chemoradiation boost and consolidation durvalumab in resectable stage III NSCLC

Kurzbeschreibung

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.

EudraCT-Nummer: 2019-000058-77

NCT-Nummer: NCT04202809

Aktueller Studienstatus: Aktiv, nicht rekrutierend

Studie aktiv in den Jahren: 2019,2020,2021,2022,2023,2024,2025

Beteiligte

Institut

Klinik und Poliklinik für Strahlentherapie
Innere Klinik (Tumorforschung)
Ruhrlandklinik - Klinik für Thoraxchirurgie und thorakale Endoskopie
Ruhrlandklinik - Thorakale Onkologie
Westdeutsches Tumorzentrum

Prüfarzt (AMG) / Studienleitung (BO)

PD Dr. med. Wilfried Eberhardt

wilfried.eberhardt@uk-essen.de

Hufelandstr. 55
45147 Essen

Sponsor

Universitätsklinik Essen (AöR)

+49 (0)201 723-0
info@uk-essen.de

Hufelandstraße 55
45147 Essen

Studiendesign

randomisiert, offen, kontrolliert, multizentrisch, national

Einschlusskriterien

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)

Ausschlusskriterien

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

19. previous immunotherapy

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, 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 immunosuppressive medication within 14 days before the first dose of durvalumab.

37. Current or prior use of immunostimulatory agents within 14 days before the first dose of durvalumab

38. Receipt of live attenuated vaccine within 90 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 90 days after the last dose of IP

39. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy

40. Known allergy or hypersensitivity to durvalumab or any excipientFor full text exclusion criteria and exceptions please refer to study protocol section 4.2

Studienteilnehmende Mindestalter

18 Jahr(e)

Studienteilnehmende Höchstalter

74 Jahr(e)

Geschlecht

Männlich/Weiblich

Indikation

Lungenkrebs

Medizinischer Befund

non-small cell lung cancer stages IIIA (N2) and selected resectable stages IIIB

MedDRA Term

Non-small cell lung cancer