Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)

NCT ID: NCT03345810

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-14
• Study Completion Date: 2022-12-31

Brief Summary

AIO-YMO/TRK-0416 (DURATION) is a open-label, treatment stratified and randomized phase II study of Durvalumab, frail or elderly patients with metastatic non-squamous NSCLC with no targetable molecular alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based standard-combination chemotherapy but eligible for at-least mono-chemotherapy with gemcitabine or vinorelbine.

Detailed Description

The primary objective is to assess the safety and tolerability of sequential therapy consisting of standard of care mono- or combination chemotherapy followed by durvalumab in comparison to standard of care mono- or combination chemotherapy in frail/elderly patients.

Conditions

Carcinoma, Non-Small-Cell Lung; Metastatic Lung Cancer; Non Small Cell Lung Cancer; Lung Adenocarcinoma Metastatic; Large Cell Lung Carcinoma Metastatic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Arm A

Frail or elderly patients with metastatic NSCLC; CARG- Score ≤ 3 Carboplatin (AUC 5.0; D1) + nab-Paclitaxel (100mg/m2 D1,D8) Q3W

Group Type: ACTIVE_COMPARATOR

nab-Paclitaxel

Intervention Type: DRUG

(100 mg/m2 intravenous infusion over 30 minutes on D1, D8) cycle Q3W

Carboplatin

Intervention Type: DRUG

(AUC = 5 mg•min/mL on Day 1) cycle Q3W

Experimental Arm B

Frail or elderly patients with metastatic NSCLC; CARG- Score ≤ 3

Induction:Carboplatin (AUC 5.0; D1) + nab-Paclitaxel (100mg/m2) D1,D8; Q3W [2 cyc] followed by durvalumab (1125 mg; Q3W) [ 2 cyc] Maintenance:durvalumab (1500 mg) Q4W

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Induction: (1125 mg) cycle Q3W Maintenance: (1500 mg) cycle Q4W

nab-Paclitaxel

Intervention Type: DRUG

(100 mg/m2 intravenous infusion over 30 minutes on D1, D8) cycle Q3W

Carboplatin

Intervention Type: DRUG

(AUC = 5 mg•min/mL on Day 1) cycle Q3W

Experimental Arm C

Frail or elderly patients with metastatic NSCLC; CARG- Score > 3

Induction: Vinorelbine (30 mg/m2; D1+D8) Q3W [ 2 cyc] or Gemcitabine (1000 mg/m2; D1+D8) Q3W [ 2 cyc] followed by durvalumab (1125 mg) Q3W [2 cyc] Maintenance:durvalumab (1500 mg; Q4W)

Group Type: EXPERIMENTAL

Durvalumab

Intervention Type: DRUG

Induction: (1125 mg) cycle Q3W Maintenance: (1500 mg) cycle Q4W

Vinorelbine

Intervention Type: DRUG

(30 mg/m2 D1 + D8 as infusion) cycle Q3W

Gemcitabine

Intervention Type: DRUG

(1000 mg/m2 D1 + D8 as infusion) cycle Q3W

Control Arm D

Frail or elderly patients with metastatic NSCLC; CARG- Score > 3

Vinorelbine (30 mg/m2; D1+D8) Q3W or Gemcitabine (1000 mg/m2; D1+D8) Q3W

Group Type: ACTIVE_COMPARATOR

Vinorelbine

Intervention Type: DRUG

(30 mg/m2 D1 + D8 as infusion) cycle Q3W

Gemcitabine

Intervention Type: DRUG

(1000 mg/m2 D1 + D8 as infusion) cycle Q3W

Interventions

Durvalumab

Induction: (1125 mg) cycle Q3W Maintenance: (1500 mg) cycle Q4W

Intervention Type: DRUG

Vinorelbine

(30 mg/m2 D1 + D8 as infusion) cycle Q3W

Intervention Type: DRUG

Gemcitabine

(1000 mg/m2 D1 + D8 as infusion) cycle Q3W

Intervention Type: DRUG

nab-Paclitaxel

(100 mg/m2 intravenous infusion over 30 minutes on D1, D8) cycle Q3W

Intervention Type: DRUG

Carboplatin

(AUC = 5 mg•min/mL on Day 1) cycle Q3W

Intervention Type: DRUG

Other Intervention Names

MEDI4736; Abraxane

Eligibility Criteria

Inclusion Criteria

1. Written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations

2. Age ≥ 70 years at time of study entry and/or Charlson-Comorbidity-Index (CCI) >1 and/or Performance status ECOG >1

3. Histologically confirmed diagnosis of metastatic NSCLC and no targetable molecular alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based standard-combination chemotherapy.

4. Patients with measurable disease (at least one uni-dimensionally measurable target lesion not previously irradiated, by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) are eligible.

5. A formalin fixed, paraffin-embedded (FFPE) tumor tissue block (fresh or archival less than 3 years old or recent) or a minimum of 10 unstained slides of tumor sample (slices must be less than 90 days old and collected on SuperFrost slides provided by the sponsor) must be available for biomarker (PD-L1) evaluation. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is inappropriate.

6. No prior chemotherapy or any other systemic therapy for metastatic NSCLC. Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced disease are eligible, provided that progression has occurred >6 months from last therapy.

7. Prior radiotherapy and surgery are allowed if completed 4 weeks (for minor surgery and palliative radiotherapy for bone pain: 2 weeks) prior to start of treatment and patient recovered from toxic effects or associated adverse events.

8. Adequate blood count, liver-enzymes, and renal function:

• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x ULN. This will not apply to subjects 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.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance

9. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, examinations including follow up and appropriate contraception

Exclusion Criteria

1. Mixed small-cell lung cancer and NSCLC histology

2. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's correction

3. History of another primary malignancy except local prostate cancer without need for systemic treatment (e.g. active surveillance, operation without need for adjuvant treatment) and malignancies treated with curative intent and with no known active disease >2 years befor the first dose of study drug and of low potential risk for recurrence, e.g. adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ)

4. Pre-existing peripheral neuropathy of Grade ≥ 2

5. Brain metastasis or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatement.

6. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

8. History of primary immunodeficiency

9. History of allogeneic organ transplant

10. History of hypersensitivity to durvalumab or any excipient

11. History of hypersensitivity to any of the comparator agents

12. Medication that is known to interfere with any of the agents applied in the trial.

13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent

14. Clinical diagnosis of active tuberculosis

15. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab

16. Male patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year)

17. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

18. Participation in another clinical study with an investigational product during the last 30 days before inclusion

19. Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab

20. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

21. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21 days prior to the first dose of study drug or ≤4 half-lifes of the agent administered, which ever comes first.

22. Previous enrollment or randomization in the present study.

23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff of sponsor and study site)

24. Patient who might be dependent on the sponsor, site or the investigator

25. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.

26. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Celgene

INDUSTRY

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonas Kuon, Dr

Role: PRINCIPAL_INVESTIGATOR

Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany

Locations

Gesundheitszentrum St. Marien GmbH

Amberg, , Germany

Ev. Lungenklinik Berlin

Berlin, , Germany

Kliniken der Stadt Köln gGmbH

Cologne, , Germany

Klinikum Darmstadt

Darmstadt, , Germany

Universitätsklinikum Carl-Gustav-Carus

Dresden, , Germany

Klinikum Esslingen

Esslingen am Neckar, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Klinik Schillerhöhe

Gerlingen, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

Onkodoc GmbH

Gütersloh, , Germany

Krankenhaus Martha-Maria Halle Dölau

Halle, , Germany

Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital

Heidelberg, , Germany

Lungenklinik Hemer

Hemer, , Germany

"Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, , Germany

Ortenau-Klinikum Lahr

Lahr, , Germany

Ev. Diakonissenkrankenhaus Leipzig

Leipzig, , Germany

Klinik Löwenstein gGmbH

Löwenstein, , Germany

Klinikum Ludwigsburg

Ludwigsburg, , Germany

DRK-Kliniken Berlin Mitte

Mitte, , Germany

Klinikum der Universität München

München, , Germany

Pius Hospital Oldenburg

Oldenburg, , Germany

Krankenhaus Barmherzige Brüder

Regensburg, , Germany

"Klinikum Rheine

Rheine, , Germany

Marienhospital

Stuttgart, , Germany

Krankenhaus der Barmherzigen Brüder

Trier, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

SHG-Kliniken-Völklingen

Völklingen, , Germany

Hämatologisch-Onkologische Praxis Würselen

Würselen, , Germany

Klinikum Würzburg Mitte gGmbH

Würzburg, , Germany

Countries

Germany

References

Kuon J, Hommertgen A, Krisam J, Lasitschka F, Stenzinger A, Blasi M, Bozorgmehr F, Maenz M, Kieser M, Schneider M, Thomas M. Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial. Trials. 2020 Apr 22;21(1):352. doi: 10.1186/s13063-020-04280-8.

Reference Type: DERIVED

PMID: 32321565 (View on PubMed)

Related Links

http://www.aio-portal.de

AIO - Working Group for Medical Oncology from the German Cancer Society

http://www.aio-studien-ggmbh.de

AIO-Studien-gGmbH

Other Identifiers

2016-003963-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESR-15-11003

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AX-CL-NSCLC-AIO-008260

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AIO-YMO/TRK-0416

Identifier Type: -

Identifier Source: org_study_id