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

NCT03345810 | Completed Phase 2

• 4 other identifiers: AIO-YMO/TRK-04162016-003963-20ESR-15-11003AX-CL-NSCLC-AIO-008260
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 30

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.

Conditions

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

Keywords

NSCLC; Non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Rate of treatment related Grade III/IV adverse events (CTCAE V4.03)

  Comparison of the outcome of sequential therapy consisting of standard of care mono- or combination chemotherapy followed by durvalumab versus standard of care mono- or combination chemotherapy in frail/elderly patients

  through study completion, an average of 24 months

Secondary Outcomes (8)

• PFS

  approx. 24 months

• ORR using assessment according to RECIST 1.1

  approx. 24 months

• OS

  approx. 60 months

• Adverse Events /Serious Adverse Events

  approx. 48 months

• Health related Quality of Life (HR-QoL)

  approx. 60 months

Study Arms (4)

Control Arm A

ACTIVE COMPARATOR

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

Drug: nab-Paclitaxel; Drug: Carboplatin

Experimental Arm B

EXPERIMENTAL

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

Drug: Durvalumab; Drug: nab-Paclitaxel; Drug: Carboplatin

Experimental Arm C

EXPERIMENTAL

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)

Drug: Durvalumab; Drug: Vinorelbine; Drug: Gemcitabine

Control Arm D

ACTIVE COMPARATOR

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

Drug: Vinorelbine; Drug: Gemcitabine

Interventions

Durvalumab DRUG

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

Also known as: MEDI4736

Experimental Arm B; Experimental Arm C

Vinorelbine DRUG

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

Control Arm D; Experimental Arm C

Gemcitabine DRUG

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

Control Arm D; Experimental Arm C

nab-Paclitaxel DRUG

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

Also known as: Abraxane

Control Arm A; Experimental Arm B

Carboplatin DRUG

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

Control Arm A; Experimental Arm B

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• Age ≥ 70 years at time of study entry and/or Charlson-Comorbidity-Index (CCI) \>1 and/or Performance status ECOG \>1
• Histologically confirmed diagnosis of metastatic NSCLC and no targetable molecular alterations (EGFRwt; ALKtransl-) and not amenable to cisplatinum-based standard-combination chemotherapy.
• 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.
• 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.
• 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.
• 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.
• 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
• 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

You may not qualify if:

• Mixed small-cell lung cancer and NSCLC histology
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's correction
• 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)
• Pre-existing peripheral neuropathy of Grade ≥ 2
• 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.
• 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.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• History of allogeneic organ transplant
• History of hypersensitivity to durvalumab or any excipient
• History of hypersensitivity to any of the comparator agents
• Medication that is known to interfere with any of the agents applied in the trial.
• 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
• Clinical diagnosis of active tuberculosis
• Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator
• Celgene: collaborator

Study Sites (30)

Gesundheitszentrum St. Marien GmbH

Amberg, 92224, Germany

Location

Ev. Lungenklinik Berlin

Berlin, 13125, Germany

Location

Kliniken der Stadt Köln gGmbH

Cologne, 51109, Germany

Location

Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

Universitätsklinikum Carl-Gustav-Carus

Dresden, 01307, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, 60590, Germany

Location

Klinik Schillerhöhe

Gerlingen, 70839, Germany

Location

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

Location

Onkodoc GmbH

Gütersloh, 33332, Germany

Location

Krankenhaus Martha-Maria Halle Dölau

Halle, 06120, Germany

Location

Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital

Heidelberg, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

"Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, 76137, Germany

Location

Ortenau-Klinikum Lahr

Lahr, 77933, Germany

Location

Ev. Diakonissenkrankenhaus Leipzig

Leipzig, 04177, Germany

Location

Klinik Löwenstein gGmbH

Löwenstein, 74245, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

DRK-Kliniken Berlin Mitte

Mitte, 13359, Germany

Location

Klinikum der Universität München

München, 81377, Germany

Location

Pius Hospital Oldenburg

Oldenburg, 26121, Germany

Location

Krankenhaus Barmherzige Brüder

Regensburg, 93049, Germany

Location

"Klinikum Rheine

Rheine, 48341, Germany

Location

Marienhospital

Stuttgart, 70199, Germany

Location

Krankenhaus der Barmherzigen Brüder

Trier, 54292, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78052, Germany

Location

SHG-Kliniken-Völklingen

Völklingen, 66333, Germany

Location

Hämatologisch-Onkologische Praxis Würselen

Würselen, 52146, Germany

Location

Klinikum Würzburg Mitte gGmbH

Würzburg, 97074, Germany

Location

Related Publications (1)

• 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.

  PMID: 32321565 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

durvalumab; Vinorelbine; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes

Study Officials

• Jonas Kuon, Dr

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

  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

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: November 17, 2017
• Study Start: December 14, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (30)