Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Thoracic Radiotherapy Plus Durvalumab in Elderly and/or Frail NSCLC Stage III Patients Unfit for Chemotherapy (TRADE-hypo)

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: NCT04351256
Recruitment Status : Recruiting
First Posted : April 17, 2020
Last Update Posted : June 30, 2020
Sponsor:
Collaborators:
Thoraxklinik-Heidelberg gGmbH
AstraZeneca
Information provided by (Responsible Party):
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

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).

Condition or disease Intervention/treatment Phase
NSCLC, Stage III Drug: Durvalumab Injection [Imfinzi] Radiation: Thoracic Radiotherapy (TRT) conventionally Radiation: Thoracic Radiotherapy (TRT) hypofractionated Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Durvalumab treatment and Thoracic Radiotherapy
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 20, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
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)
Drug: Durvalumab Injection [Imfinzi]
Durvalumab fixed dose of 1,500 mg

Radiation: Thoracic Radiotherapy (TRT) hypofractionated
Hypofractionated TRT consisting of 20 x 2,75 Gy (55 Gy) within 4 weeks

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)
Drug: Durvalumab Injection [Imfinzi]
Durvalumab fixed dose of 1,500 mg

Radiation: Thoracic Radiotherapy (TRT) conventionally
Conventionally fractionated TRT consisting of 30 x 2 Gy (60 Gy) within 6 weeks




Primary Outcome Measures :
  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 Measures :
  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%)


Other Outcome Measures:
  1. Vulnerability assessment based on the G8-screening questionnaire [ Time Frame: up to 35 months ]
    Vulnerability assessment based on the G8-screening questionnaire and its association to survival and outcome



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≥ 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 ( 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 ≥ 5 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

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): NCT04351256


Contacts
Layout table for location contacts
Contact: Farastuk Bozorgmehr, Dr. med. +49 6221-396 8077 farastuk.bozorgmehr@med.uni-heidelberg.de
Contact: Johanna Riedel, Dr. rer. med. riedel.johanna@ikf-khnw.de

Locations
Layout table for location information
Germany
Onkodok GmbH Recruiting
Gütersloh, Germany, 33332
Contact: Philipp Schütt, Dr.         
Thoraxklinik am Universitätsklinikum Heidelberg Recruiting
Heidelberg, Germany, 69126
Contact: Farastuk Bozorgmehr, Dr.    +49 6221 396 ext 8807    farastuk.bozorgmehr@med.uni-heidelberg.de   
Lungenklinik Hemer, Pneumologie und Thorakale Onkologie Recruiting
Hemer, Germany, 58675
Principal Investigator: Thomas Wehler, MD         
Vincentius-Diakonissen-Kliniken gAG Recruiting
Karlsruhe, Germany, 76137
Contact: Christian Meyer zum Büschenfelde, Prof. Dr.         
Kliniken der Stadt Köln gGmbH, Lungenklinik Merheim Recruiting
Köln, Germany, 51109
Contact: Jessica Jürgens         
Klinikum Ludwigsburg Recruiting
Ludwigsburg, Germany, 71640
Contact: Matthias Ulmer, Dr.         
Universitätsmedizin Mainz Recruiting
Mainz, Germany, 55131
Contact: Jürgen Alt, Dr.         
Sponsors and Collaborators
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Thoraxklinik-Heidelberg gGmbH
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Farastuk Bozorgmehr, Dr. med. Dept. of Thoracic Oncology Thoraxklinik at Heidelberg University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
ClinicalTrials.gov Identifier: NCT04351256    
Other Study ID Numbers: TRADE-hypo
2019-002192-33 ( EudraCT Number )
AIO-YMO/TRK-0319 ( Other Identifier: AIO )
ESR-18-13893 ( Other Grant/Funding Number: AstraZeneca )
First Posted: April 17, 2020    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020
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
Keywords provided by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest:
Durvalumab
Thoracic Radiotherapy
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