Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase-II Trial of Induction Chemotherapy and Chemoradiotherapy Plus/Minus Durvalumab and Consolidation Immunotherapy in Patients With Resectable Stage III NSCLC. (ESPADURVA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04202809
Recruitment Status : Recruiting
First Posted : December 18, 2019
Last Update Posted : August 30, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Essen

Brief Summary:
To compare a complex induction multimodality protocol (ESPATUE) + concurrent immunotherapy with PD-L1 antibody Durvalumab given every three weeks to the same induction multimodality protocol without Durvalumab immunotherapy induction followed by definitive local treatment (surgery for those considered resectable or chemoradiation boost for those not considered to be R0-resectable) followed by consolidation Durvalumab treatment in both arms.

Condition or disease Intervention/treatment Phase
NSCLC, Stage III Drug: Durvalumab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : January 13, 2020
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Chemo- and Radiochemotherapy + Durvalumab Drug: Durvalumab
Durvalumab is given earlier as registered, during chemotherapy and radiotherapy in treatment Arm A

No Intervention: Chemo- and Radiochemotherapy



Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 2 years ]
    Two-year progression-free survival rate


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: after 1, 2, 3, 4 and 5 years ]
  2. 2-y-overall survival rate [ Time Frame: 2 years ]
  3. Functional response [ Time Frame: Week 15 ]
    to investigate functional response (PET-CT-scan) to induction therapy prior to thoracotomy

  4. RECIST response (induction) [ Time Frame: Week 9 ]
    to investigate RECIST response to induction therapy in the whole Population and in both arms.

  5. RECIST criteria [ Time Frame: Through study completion, an average of every 2 months for up to 11 months ]
    Radiological response

  6. EORTC QLQ-C30 [ Time Frame: Through study completion, an average of every 6 weeks for up to 11 months ]
    Quality of life (QLQ-C30)

  7. EORTC QLQ-LC13 [ Time Frame: Through study completion, an average of every 6 weeks for up to 11 months ]
    Quality of life (QLQ-Lung Cancer 13(LC13))

  8. FACT-L [ Time Frame: Through study completion, an average of every 6 weeks for up to 11 months ]
    Quality of life (Functional Assessment of Cancer Therapy-Lung (FACT-L))



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:
  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 European Respiratory Society (ERS)/European Society of Thoracic Surgeons (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
  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. The following age-specific requirements apply:
  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 according to New York Heart Association (NYHA) III-IV).

Exclusion Criteria:

  1. resectable IIB or selected IIIA (T3N0; T3N1)
  2. unresectable disease pre-treatment
  3. mixed histology with areas of small cell carcinoma (neuroendocrine markers)
  4. clinically symptomatic vena cava superior syndrome
  5. diffuse mediastinal involvement
  6. patients with T3N3 and T4N3 tumors (IIIC according to International Association for the Study of Lung Cancer (IASLC)/Union Internationale Contre le Cancer (UICC) 8)
  7. invasion of the thoracic aorta (T4 - aorta)
  8. invasion of the heart (except left atrium - T4 - heart)
  9. invasion of the esophagus (T4 - esophagus)
  10. invasion of spine (T4 - spine)
  11. (full blown) Pancoast-syndrome in tumors of the superior sulcus (T3-4 Nx)
  12. malignant (positive) pericardial effusion (M1a - pericardial effusion)
  13. malignant (positive) pleural effusion (M1a - pleural effusion)
  14. involvement of the contralateral hilar nodes (if any data available)
  15. endobronchial tumor extension to the contralateral main stem bronchus
  16. ipsi- or contralateral supraclavicular nodes (N3 - 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 (e.g. symptomatic psychiatric disorder)
  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 (non-interventional) 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 Adverse Event (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 (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT scan
  27. Any concurrent chemotherapy, Intraperitoneal (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.
  28. Major surgical procedure (as defined by the Investigator) 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 (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive Hepatitis B Virus (HBV) surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV ½ antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) 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 excipient

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04202809


Contacts
Layout table for location contacts
Contact: Jan Ellermeier, PhD 0049 201 72377412 ext 77412 jan.ellermeier@uk-essen.de

Locations
Layout table for location information
Germany
Universitätsklinikum Essen Recruiting
Essen, Germany, 45147
Universitätsklinikum Freiburg Not yet recruiting
Freiburg, Germany, 79106
Pius-Hospital Oldenburg Recruiting
Oldenburg, Germany, 26121
Robert-Bosch-Krankenhaus Recruiting
Stuttgart, Germany, 70376
Sponsors and Collaborators
University Hospital, Essen
Investigators
Layout table for investigator information
Principal Investigator: Wilfried Eberhardt, PD MD University Hospital, Essen
Layout table for additonal information
Responsible Party: University Hospital, Essen
ClinicalTrials.gov Identifier: NCT04202809    
Other Study ID Numbers: ESPADURVA
First Posted: December 18, 2019    Key Record Dates
Last Update Posted: August 30, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents