Clinical trial NCT03345810: Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)
Official title: Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: AIO-Studien-gGmbH
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Celgene
First posted: 2017-11-17
Enrollment: 200
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\].

Primary outcomes:
measure: Rate of treatment related Grade III/IV adverse events (CTCAE V4.03)
timeFrame: through study completion, an average of 24 months
Secondary outcomes:
measure: PFS
timeFrame: approx. 24 months
measure: ORR using assessment according to RECIST 1.1
timeFrame: approx. 24 months
measure: OS
timeFrame: approx. 60 months
measure: Adverse Events /Serious Adverse Events
timeFrame: approx. 48 months
measure: Health related Quality of Life (HR-QoL)
timeFrame: approx. 60 months
measure: Geriatric assessment
timeFrame: approx. 60 months
measure: Geriatric assessment
timeFrame: approx. 60 months
measure: Geriatric assessment
timeFrame: approx. 60 months
Other outcomes:
Locations:
city: Amberg
country: Germany
facility: Gesundheitszentrum St. Marien GmbH
city: Berlin-Mitte
country: Germany
facility: DRK-Kliniken Berlin Mitte
city: Berlin
country: Germany
facility: Ev. Lungenklinik Berlin
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
city: Dresden
country: Germany
facility: Universitätsklinikum Carl-Gustav-Carus
city: Esslingen
country: Germany
facility: Klinikum Esslingen
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Gerlingen
country: Germany
facility: Klinik Schillerhöhe
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Gütersloh
country: Germany
facility: Onkodoc GmbH
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle Dölau
city: Heidelberg
country: Germany
facility: Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Karlsruhe
country: Germany
facility: "Vincentius-Diakonissen-Kliniken gAG
city: Köln
country: Germany
facility: Kliniken der Stadt Köln gGmbH
city: Lahr
country: Germany
facility: Ortenau-Klinikum Lahr
city: Leipzig
country: Germany
facility: Ev. Diakonissenkrankenhaus Leipzig
city: Ludwigsburg
country: Germany
facility: Klinikum Ludwigsburg
city: Löwenstein
country: Germany
facility: Klinik Löwenstein gGmbH
city: München
country: Germany
facility: Klinikum der Universität München
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder
city: Rheine
country: Germany
facility: "Klinikum Rheine
city: Stuttgart
country: Germany
facility: Marienhospital
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Völklingen
country: Germany
facility: SHG-Kliniken-Völklingen
city: Würselen
country: Germany
facility: Hämatologisch-Onkologische Praxis Würselen
city: Würzburg
country: Germany
facility: Klinikum Würzburg Mitte gGmbH
Study officials:
affiliation: Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany
name: Jonas Kuon, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.