Immunochemotherapy, Surgery or Chemoradiation, and Durvalumab for Stage IIIA/B NSCLC

NCT06810609 | Recruiting Phase 2 DMC

• 2 other identifiers: ESR-21-215652024-516367-80-00
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 5

Brief Summary

The hypothesis of the study is that induction immunochemotherapy, followed by surgery or chemoradiation and consolidation Durvalumab immunotherapy, can significantly improve event-free survival in patients with resectable or borderline resectable NSCLC at stage IIIA/B compared to existing treatment methods.

Conditions

Lung Cancer Non-Small Cell Cancer (NSCLC)

Keywords

InDuRanS; Non-Small Cell Lung Cancer; Chemoradiation; Resectable NSCLC; Durvalumab; Induction Immunochemotherapy

Outcome Measures

Primary Outcomes (1)

• 2-Year Event-Free Survival (EFS) Rate in Patients with Resectable or Borderline Resectable NSCLC

  2 year EFS rate is defined as percentage of patients without an event specified as relapse or progression according to RECIST 1.1 criteria, secondary tumor, or death of any cause, whichever occurs first, within 2 years after date of randomization.

  Within 2 years after date of randomization

Secondary Outcomes (13)

• Analyze the health-related Quality of Life (QoL)

  from date of randomization through study completion (an average of 14 months after randomization)

• Analyze the health-related Quality of Life (QoL)

  from date of randomization through study completion (an average of 14 months after randomization)

• Occurence of adverse events

  for 12 months according to arm

• Efficacy of multimodality treatment

  From Randomization to death from any cause, within 2 years after date of randomization or throughout extended follow-up

• Efficacy of multimodality treatment

  From Randomization to objective disease progression, within 2 years after date of randomization or throughout extended follow-up

Other Outcomes (5)

• Radiological response including radiomics in irradiated patients.

  from randomization into arm 2 (chemoradiotherapy) till study completion (an average of 14 months after randomization) or throughout extended follow-up

• Training and evaluation of deep learning algorithms for automated response prediction

  from enrollment till study completion (an average of 17 months after enrollment) or throughout extended follow-up

• Training and evaluation of deep learning algorithms for automated assessment of Tumor Progression Patterns

  from enrollment till study completion (an average of 17 months after enrollment) or throughout extended follow-up

Study Arms (2)

Surgery + Immunotherapy

EXPERIMENTAL

Surgical removal of metastasis and consolidation Durvalumab immunotherapy.

Procedure: surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines; Drug: Immunotherapy

Chemoradiotherapy + Immunotherapy

EXPERIMENTAL

Chemoradiotherapy (CRT) followed by consolidation immunotherapy with Durvalumab .

Radiation: Chemoradiotherapy; Drug: Immunotherapy

Interventions

Chemoradiotherapy RADIATION

Chemoradiotherapy

Chemoradiotherapy + Immunotherapy

Immunotherapy DRUG

Immunotherapy (Durvalumab).

Chemoradiotherapy + Immunotherapy; Surgery + Immunotherapy

surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelines PROCEDURE

Surgical removal of the tumor in patients with resectable or borderline resectable NSCLC

Surgery + Immunotherapy

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patient is 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 (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.
• \. Patient is willing and able to comply with the protocol for the duration of the study 3. Age ≥ 18 years and \< 75 years. 4. All sex and gender. 5. Female patients of childbearing potential as well as male patients with partners of childbearing potential must agree to always use a highly effective form of contraception according to the Clinical Trials Facilitation and Coordination Group (CTFG) during the course of this study and for at least 90 days after the last dose of durvalumab or 6 months after the last dose of chemotherapy, whichever occurs last.
• \. Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause.
• \. Histologically and / or cytologically proven NSCLC (EGFRm-, ALK-). 8.
• Selected patients with NSCLC stage IIIA/B:
• IIIA: one or more lymph node levels involved at EBUS/mediastinoscopy T1/T2 N2.
• \. Life expectancy of \> 12 weeks. 14. Body weight \> 30 kg. 15.
• Adequate normal organ and bone marrow function as defined below:
• a. Hemoglobin ≥ 9.0 g/dL. b. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L. c. Platelet count ≥ 100 × 109/L. d. Serum bilirubin ≤ 1.5 × 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.
• e. Alanine aminotransferase (ALT/SGPT) and aspartate aminotransferase (AST/SGOT) ≤ 2.5 × institutional ULN.
• f. Measured creatinine clearance (CL) ≥ 60 mL/min or calculated creatinine CL ≥ 60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
• \. Stable cardiac function (no myocardial infarction (MI) within 6 months, no heart failure NYHA III-IV).
• \. Discussion in a multidisciplinary tumor board which supports participation in this clinical trial, indicating that both chemoradiotherapy and surgery are possible local treatments.
• Given technical/oncologic complete resectability (R0) at the time of randomization.
• Sufficient functional reserves for the planned surgery

You may not qualify if:

• \. Prior treatments including prior mediastinal irradiation. 13. Insufficient patients' compliance (e.g., symptomatic psychiatric disorder) or missing written informed consent or definitive refusal for participation.
• \. Prior randomization of treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
• Patients who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy.
• NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to be enrolled if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• 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.
• \. Participation in another clinical study with an investigational product during the last 12 months.
• \. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• \. 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.
• \. Any concurrent chemotherapy (other than study therapy), Investigational Product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• \. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of durvalumab.
• \. History of allogenic organ transplantation or a stem cell transplantation. 22.
• 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 \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (5)

University Hospital Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

RECRUITING

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70174, Germany

RECRUITING

University Hospital Gießen

Giessen, Hesse, 35392, Germany

NOT YET RECRUITING

Johannes Wesling Klinikum Minden Mühlenkreiskliniken, Hämatologie und Onkologie

Minden, North Rhine-Westphalia, 32429, Germany

RECRUITING

University Hospital Bonn

Bonn, 53127, Germany

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Surgical Procedures, Operative; Chemoradiotherapy; Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Immunomodulation; Biological Therapy

Central Study Contacts

Eleni Gkika, Prof. Dr. med.

CONTACT

0049 22825710353; eleni.gkika@ukbonn.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: The study involves randomizing participants to different treatment arms (induction immunochemotherapy, followed by surgery or chemoradiation, and then consolidation Durvalumab immunotherapy), with the goal of comparing the outcomes between those receiving the full treatment regimen and other treatment options.

Study Record Dates

• First Submitted: January 24, 2025
• First Posted: February 5, 2025
• Study Start: April 20, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: January 27, 2026

Record last verified: 2025-05

Locations

DE (5)