Thoracic Radiotherapy Plus Durvalumab in Elderly and/or Frail NSCLC Stage III Patients Unfit for Chemotherapy

NCT04351256 | Completed Phase 2 DMC

• 5 other identifiers: TRADE-hypo2019-002192-33AIO-YMO/TRK-0319ESR-18-138932024-513948-28-00
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 14

Brief Summary

This is a randomized, open-label, multicenter, phase II trial investigating the combination of thoracic radiotherapy plus Durvalumab in patients with locally advanced, unresectable NSCLC (stage III) that are unfit for chemotherapy (e.g. due to age and/or frailty).

Conditions

NSCLC, Stage III

Keywords

Durvalumab; Thoracic Radiotherapy

Outcome Measures

Primary Outcomes (2)

• Toxicity (pneumonitis)

  Toxicity, defined by the occurence of treatment-related pneumonitis grade ≥ 3

  up to 35 months

• Objective response

  Objective response evaluated at 12 weeks (3 months) after first durvalumab administration according to RECIST 1.1 criteria

  up to 35 months

Secondary Outcomes (8)

• treatment-related AEs and SAEs

  up to 35 months

• frequency of abnormal laboratory parameters (hematology panel, chemistry panel, Thyroid-stimulating hormone (TSH))

  up to 35 months

• Progression Free Survival (PFS)

  up to 35 months

• Duration of Clinical Benefit

  up to 35 months

• Metastasis-Free Survival (MFS)

  up to 35 months

Other Outcomes (1)

• Vulnerability assessment based on the G8-screening questionnaire

  up to 35 months

Study Arms (2)

Arm A (HYPO group)

EXPERIMENTAL

* Durvalumab at a fixed dose of 1,500 mg as an IV infusion over 1 hour, on day 1, to be repeated every 4 weeks (Q4W) for a maximum of 12 cycles * Thoracic radiation therapy (TRT): hypofractionated thoracic radiotherapy consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks (+9 days)

Drug: Durvalumab Injection [Imfinzi]; Radiation: Thoracic Radiotherapy (TRT) hypofractionated

Arm B (CON group)

ACTIVE COMPARATOR

* Durvalumab at a fixed dose of 1,500 mg as an IV infusion over 1 hour, on day 1, to be repeated every 4 weeks (Q4W) for a maximum of 12 cycles * Thoracic radiation therapy (TRT): conventional fractions of 30 x 2 Gy (60 Gy) within 6 weeks (+9 days)

Drug: Durvalumab Injection [Imfinzi]; Radiation: Thoracic Radiotherapy (TRT) conventionally

Interventions

Durvalumab Injection [Imfinzi] DRUG

Durvalumab fixed dose of 1,500 mg

Arm A (HYPO group); Arm B (CON group)

Thoracic Radiotherapy (TRT) conventionally RADIATION

Conventionally fractionated TRT consisting of 30 x 2 Gy (60 Gy) within 6 weeks

Arm B (CON group)

Thoracic Radiotherapy (TRT) hypofractionated RADIATION

Hypofractionated TRT consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks

Arm A (HYPO group)

Eligibility Criteria

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

You may qualify if:

• Fully-informed written consent and 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.
• Age ≥ 18 years.
• Histologically documented diagnosis of unresectable stage III NSCLC.
• Non-feasibility of sequential chemo-/radiotherapy as determined by the site's multi-disciplinary tumor board; if there is no tumor board, then this decision will be made by the investigator in consultation with a radiation oncologist, if the investigator is not a radiation oncologist; or by the investigator in consultation with an oncologist, if the investigator is not an oncologist.
• Fulfills at least one of the following criteria:
• Performance status (PS) 2 (ECOG scale)
• ECOG 1 and CCI ≥ 1
• Age ≥ 70 years
• Must have a life expectancy of at least 12 weeks.
• FEV1 ≥ 40%
• DLCO or DLCO/VA (Hb-corrected, if available) ≥ 40%
• FVC or VC ≥ 70%
• At least one measurable site of disease as defined by RECIST 1.1
• Adequate bone marrow and renal function including the following:
• Hemoglobin ≥ 9.0 g/dL;

You may not qualify if:

• 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.
• Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
• Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1),anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines.
• History or current radiology suggestive of interstitial lung disease.
• Oxygen-dependent medical condition.
• Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable.
• Prior thoracic radiotherapy within the past 5 years before the first dose of study drug.
• Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent is acceptable.
• Active or prior documented autoimmune or inflammatory disorders (except inflammatory bowel disease \[e.g. ulcerative colitis or Crohn's disease\]; ( including diverticulitis \[with the exception of diverticulosis\], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener's syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
• Active, uncontrolled inflammatory bowel disease \[e.g. ulcerative colitis or Crohn's disease\]. Patients in stable remission for more than 1 year may be included.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease, 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.

Sponsors & Collaborators

• Thoraxklinik-Heidelberg gGmbH: collaborator
• AstraZeneca: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (14)

Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

DRK Kliniken Berlin-Mitte

Berlin, 13359, Germany

Location

Kliniken der Stadt Köln gGmbH, Lungenklinik Merheim

Cologne, 51109, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Onkodok GmbH

Gütersloh, 33332, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer, Pneumologie und Thorakale Onkologie

Hemer, 58675, Germany

Location

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76137, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Kliniken Maria Hilf GmbH

Mönchengladbach, 41063, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, 48153, Germany

Location

Sana Klinikum Offenbach GmbH

Offenbach, 63069, Germany

Location

Pi.Tri-Studien GmbH

Offenburg, 77654, Germany

Location

Related Publications (1)

• Bozorgmehr F, Chung I, Christopoulos P, Krisam J, Schneider MA, Bruckner L, Mueller DW, Thomas M, Rieken S. Thoracic radiotherapy plus Durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy - employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy: study protocol of the TRADE-hypo trial. BMC Cancer. 2020 Aug 26;20(1):806. doi: 10.1186/s12885-020-07264-8.

  PMID: 32842974 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Farastuk Bozorgmehr, Dr. med.

  Dept. of Thoracic Oncology Thoraxklinik at Heidelberg University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Durvalumab treatment and Thoracic Radiotherapy

Study Record Dates

• First Submitted: February 29, 2020
• First Posted: April 17, 2020
• Study Start: May 20, 2020
• Primary Completion: January 21, 2026
• Study Completion: January 21, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)