JOURNAL ONKOLOGIE – STUDIE

TRADE-hypo

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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04351256

Studienbeginn:
Mai 2020

Letztes Update:
21.07.2023

Wirkstoff:
Durvalumab Injection [Imfinzi]

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Collaborator:
Thoraxklinik-Heidelberg gGmbH, AstraZeneca,

Studienleiter

Farastuk Bozorgmehr, Dr. med.
Principal Investigator
Dept. of Thoracic Oncology Thoraxklinik at Heidelberg University

Kontakt

Farastuk Bozorgmehr, Dr. med.
Kontakt:
Phone: +49 6221-396 8077
E-Mail: farastuk.bozorgmehr@med.uni-heidelberg.de» Kontaktdaten anzeigen

Johanna Riedel, Dr. rer. med.
Kontakt:
E-Mail: riedel.johanna@ikf-khnw.de» Kontaktdaten anzeigen

Studienlocations
(3 von 14)

Universitätsklinikum Aachen
52074 Aachen
GermanyRekrutierend» Google-Maps

DRK Kliniken Berlin-Mitte
13359 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps

Brustzentrum der Universitätsmedizin Göttingen
Robert-Koch-Straße 40
37075 Göttingen
DeutschlandRekrutierend» Google-Maps

Onkodok GmbH
33332 Gütersloh
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Thoraxklinik am Universitätsklinikum Heidelberg
69126 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Farastuk Bozorgmehr, Dr.
Phone: +49 6221 396
Phone (ext.): 8807
E-Mail: farastuk.bozorgmehr@med.uni-heidelberg.de» Ansprechpartner anzeigen

Lungenklinik Hemer, Pneumologie und Thorakale Onkologie
58675 Hemer
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Vincentius-Diakonissen-Kliniken gAG
76137 Karlsruhe
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Kliniken der Stadt Köln gGmbH, Lungenklinik Merheim
51109 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Klinikum Ludwigsburg
71640 Ludwigsburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Darmkrebszentrum der Universitätsmedizin Mainz
Langenbeckstraße 1
55131 Mainz
DeutschlandRekrutierend» Google-Maps

Darmzentrum der Kliniken Maria Hilf GmbH Mönchengladbach
Sandradstraße 43
41061 Mönchengladbach
DeutschlandRekrutierend» Google-Maps

Gemeinschaftspraxis für Hämatologie und Onkologie
48153 Münster
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Sana Klinikum Offenbach GmbH
63069 Offenbach
(Hessen)
GermanyRekrutierend» Google-Maps

Pi.Tri-Studien GmbH
77654 Offenburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. 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.

2. Age ≥ 18 years.

3. Histologically documented diagnosis of unresectable stage III NSCLC.

4. 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.

5. Fulfills at least one of the following criteria:

- Performance status (PS) 2 (ECOG scale)

- ECOG 1 and CCI ≥ 1

- Age ≥ 70 years

6. Must have a life expectancy of at least 12 weeks.

7. FEV1 ≥ 40%

8. DLCO or DLCO/VA (Hb-corrected, if available) ≥ 40%

9. FVC or VC ≥ 70%

10. At least one measurable site of disease as defined by RECIST 1.1

11. 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

12. 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

13. Female patients with reproductive potential must have a negative urine or serum

pregnancy test within 7 days prior to start of trial.

14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for

female pre-menopausal patients.

15. 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.

Exclusion Criteria:

1. 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.

2. Participation in another clinical study with an investigational product within 21 days

prior to the first dose of the study treatment.

3. 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.

4. History or current radiology suggestive of interstitial lung disease.

5. Oxygen-dependent medical condition.

6. 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.

7. Prior thoracic radiotherapy within the past 5 years before the first dose of study

drug.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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

Studien-Rationale

Primary outcome:

1. Toxicity (pneumonitis) (Time Frame - up to 35 months):
Toxicity, defined by the occurence of treatment-related pneumonitis grade ≥ 3

2. Objective response (Time Frame - up to 35 months):
Objective response evaluated at 12 weeks (3 months) after first durvalumab administration according to RECIST 1.1 criteria

Secondary outcome:

1. treatment-related AEs and SAEs (Time Frame - up to 35 months):
Occurence of treatment-related AEs and SAEs according to CTCAE V5.0

2. frequency of abnormal laboratory parameters (hematology panel, chemistry panel, Thyroid-stimulating hormone (TSH)) (Time Frame - up to 35 months):
Frequency of abnormal values of laboratory parameters

3. Progression Free Survival (PFS) (Time Frame - up to 35 months):
PFS according to RECIST 1.1

4. Duration of Clinical Benefit (Time Frame - up to 35 months):
Duration of Clinical Benefit (Duration of Complete Response (CR), Partial Response (PR), Stable Disease (SD)) according to RECIST 1.1

5. Metastasis-Free Survival (MFS) (Time Frame - up to 35 months):
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

6. Overall survival (Time Frame - up to 35 months):
time from the date of treatment allocation to the date of death

7. Quality of Life (FACT-L) (Time Frame - up to 35 months):
measured by FACT-L questionnaire

8. objective response rate (Time Frame - up to 35 months):
Descriptive sub-group analyses of efficacy in relation to PD-L1 expression levels (<°1% vs ≥°1%)

Studien-Arme

Experimental: Arm A (HYPO group)
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)
Active Comparator: Arm B (CON group)
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)

Geprüfte Regime

Durvalumab Injection [Imfinzi]:
Durvalumab fixed dose of 1,500 mg
Thoracic Radiotherapy (TRT) conventionally:
Conventionally fractionated TRT consisting of 30 x 2 Gy (60 Gy) within 6 weeks
Thoracic Radiotherapy (TRT) hypofractionated:
Hypofractionated TRT consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks

Quelle: ClinicalTrials.gov

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