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NSCLC, Stage IIIPhase 2TRADE-hypoNCT04351256

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

A Phase 2 study testing Durvalumab Injection [Imfinzi], Thoracic Radiotherapy (TRT) conventionally and Thoracic Radiotherapy (TRT) hypofractionated in people with NSCLC, Stage III, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 14 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC, Stage III
What is being tested?
Durvalumab Injection [Imfinzi], Thoracic Radiotherapy (TRT) conventionally and Thoracic Radiotherapy (TRT) hypofractionated
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
14 sitesGermany
Study dates
20 May 2020to 21 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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;
  • absolute neutrophil count ≥ 1.0 x 103/L;
  • platelets ≥75x 109/L;
  • Calculated creatinine clearance ≥30 mL/min as determined by the Cockcroft-Gault equation
  • Adequate hepatic function (with stenting for any obstruction, if required) including the following:
  • Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN);
  • AST (SGOT) / ALT (SGPT) ≤ 2.5x institutional ULN
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
  • The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.

Who cannot join

  • 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.
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  • 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.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of IMP and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Germany14 sites

  • Universitätsklinikum Aachen

    Aachen, 52074

  • DRK Kliniken Berlin-Mitte

    Berlin, 13359

  • Kliniken der Stadt Köln gGmbH, Lungenklinik Merheim

    Cologne, 51109

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Onkodok GmbH

    Gütersloh, 33332

  • Thoraxklinik am Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Lungenklinik Hemer, Pneumologie und Thorakale Onkologie

    Hemer, 58675

  • Vincentius-Diakonissen-Kliniken gAG

    Karlsruhe, 76137

  • Klinikum Ludwigsburg

    Ludwigsburg, 71640

  • Universitätsmedizin Mainz

    Mainz, 55131

  • Kliniken Maria Hilf GmbH

    Mönchengladbach, 41063

  • Gemeinschaftspraxis für Hämatologie und Onkologie

    Münster, 48153

  • Sana Klinikum Offenbach GmbH

    Offenbach, 63069

  • Pi.Tri-Studien GmbH

    Offenburg, 77654

Other trials in Germany

About this study

Official title: Thoracic Radiotherapy Plus Durvalumab in Elderly and/or Frail NSCLC Stage III Patients Unfit for Chemotherapy - Employing Optimized (Hypofractionated) Radiotherapy to Foster Durvalumab Efficacy

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).

Read the detailed description

This trial investigates the feasibility and treatment efficacy when combining durvalumab treatment with either conventionally fractionated (CON-group) or hypofractionated thoracic radiotherapy (HYPO-group) in previously untreated NSCLC stage III patients prone to radiotherapy only.

A safety lead-in phase with stop-and-go design will precede full enrollment into the HYPO-group.

Tumor tissue as well as blood and stool samples will be collected for future biomarker analysis.

It is hypothesized that TRT combined with concurrent durvalumab administration in patients with unresectable stage III NSCLC, who are not amenable to sequential radio-/chemotherapy

  1. is safe and feasible,
  2. will improve treatment efficacy by a synergistic effect of checkpoint inhibition and the photon-induction of immunostimulatory pathways.
  3. will have an effect on the immunological characteristics of the tumor, the microenvironment, and the systemic immune response, such as upregulation of PD-L1 or secretion of stimulatory cytokines and recruitment and priming of immunocompetent cells, which might then mediate the "abscopal effect" beyond the irradiated targets.
Being tested
Durvalumab Injection [Imfinzi], Thoracic Radiotherapy (TRT) conventionally, Thoracic Radiotherapy (TRT) hypofractionated
Keywords
Durvalumab, Thoracic Radiotherapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab Injection [Imfinzi]Drug

    Durvalumab fixed dose of 1,500 mg

  • Thoracic Radiotherapy (TRT) conventionallyRadiation

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

  • Thoracic Radiotherapy (TRT) hypofractionatedRadiation

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

Study groups in NCT04351256
Study groupRoleWhat they receive
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)
Receives: 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)
Receives: Drug: Durvalumab Injection [Imfinzi]; Radiation: Thoracic Radiotherapy (TRT) conventionally

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity (pneumonitis)

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

    Measured: up to 35 months

  2. Objective response

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

    Measured: up to 35 months

Secondary outcomes (8)

  1. treatment-related AEs and SAEs

    Occurence of treatment-related AEs and SAEs according to CTCAE V5.0

    Measured: up to 35 months

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

    Frequency of abnormal values of laboratory parameters

    Measured: up to 35 months

  3. Progression Free Survival (PFS)

    PFS according to RECIST 1.1

    Measured: up to 35 months

  4. Duration of Clinical Benefit

    Duration of Clinical Benefit (Duration of Complete Response (CR), Partial Response (PR), Stable Disease (SD)) according to RECIST 1.1

    Measured: up to 35 months

  5. Metastasis-Free Survival (MFS)

    Time from the date of allocation / randomization to the date of first observed metastatic lesion (investigator assessment according to RECIST 1.1) or death from any cause

    Measured: up to 35 months

  6. Overall survival

    time from the date of treatment allocation to the date of death

    Measured: up to 35 months

  7. Quality of Life (FACT-L)

    measured by FACT-L questionnaire

    Measured: up to 35 months

  8. objective response rate

    Descriptive sub-group analyses of efficacy in relation to PD-L1 expression levels (<°1% vs ≥°1%)

    Measured: up to 35 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2020
  2. Study start20 May 2020
  3. Primary completion21 Jan 2026
  4. Study completion21 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Durvalumab treatment and Thoracic Radiotherapy
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04351256
Sponsor's protocol ID
TRADE-hypo
Other IDs
2019-002192-33, AIO-YMO/TRK-0319, ESR-18-13893, 2024-513948-28-00, 2019
Acronym
TRADE-hypo
Status last verified
Mar 2026
First submitted
29 Feb 2020
Last updated
27 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32842974

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab Injection [Imfinzi], Thoracic Radiotherapy (TRT) conventionally and Thoracic Radiotherapy (TRT) hypofractionated in people with NSCLC, Stage III, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 14 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity (pneumonitis) (time frame: up to 35 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04351256, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.

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