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

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: NCT03345810
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : July 30, 2018
Sponsor:
Collaborators:
AstraZeneca
Celgene
Information provided by (Responsible Party):
AIO-Studien-gGmbH

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Metastatic Lung Cancer Non Small Cell Lung Cancer Lung Adenocarcinoma Metastatic Large Cell Lung Carcinoma Metastatic Drug: Durvalumab Drug: Vinorelbine Drug: Gemcitabine Drug: nab-Paclitaxel Drug: Carboplatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)
Actual Study Start Date : December 14, 2017
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Active Comparator: 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
Drug: nab-Paclitaxel
(100 mg/m2 intravenous infusion over 30 minutes on D1, D8) cycle Q3W
Other Name: Abraxane

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

Experimental: 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

Drug: Durvalumab
Induction: (1125 mg) cycle Q3W Maintenance: (1500 mg) cycle Q4W
Other Name: MEDI4736

Drug: nab-Paclitaxel
(100 mg/m2 intravenous infusion over 30 minutes on D1, D8) cycle Q3W
Other Name: Abraxane

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

Experimental: 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)

Drug: Durvalumab
Induction: (1125 mg) cycle Q3W Maintenance: (1500 mg) cycle Q4W
Other Name: MEDI4736

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

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

Active Comparator: 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

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

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




Primary Outcome Measures :
  1. Rate of treatment related Grade III/IV adverse events (CTCAE V4.03) [ Time Frame: through study completion, an average of 24 months ]
    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


Secondary Outcome Measures :
  1. PFS [ Time Frame: approx. 24 months ]
    Progression Free Survival

  2. ORR using assessment according to RECIST 1.1 [ Time Frame: approx. 24 months ]
    Response Evaluation Criteria In Solid Tumors (RECIST)

  3. OS [ Time Frame: approx. 60 months ]
    Overall Survival

  4. Adverse Events /Serious Adverse Events [ Time Frame: approx. 48 months ]
    Adverse Events: Type, incidence, and severity according to NCI CTCAE version 4.03

  5. Health related Quality of Life (HR-QoL) [ Time Frame: approx. 60 months ]
    as determined with FACT-L (Functional Assessment of Cancer Therapy - Lung)

  6. Geriatric assessment [ Time Frame: approx. 60 months ]
    G8-questionnaire

  7. Geriatric assessment [ Time Frame: approx. 60 months ]
    Timed up & go (test of basic functional mobility)

  8. Geriatric assessment [ Time Frame: approx. 60 months ]
    6MWT (6 minutes walk test)



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.


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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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].

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): NCT03345810


Contacts
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Contact: Magda Krejczy +49 30 8145 344 40 magda.krejczy@aio-studien-ggmbh.de
Contact: Jonas Kuon, Dr jonas.kuon@med.uni-heidelberg.de

Locations
Show Show 30 study locations
Sponsors and Collaborators
AIO-Studien-gGmbH
AstraZeneca
Celgene
Investigators
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Principal Investigator: Jonas Kuon, Dr Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany
Additional Information:
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Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT03345810    
Other Study ID Numbers: AIO-YMO/TRK-0416
2016-003963-20 ( EudraCT Number )
ESR-15-11003 ( Other Grant/Funding Number: AstraZeneca GmbH )
AX-CL-NSCLC-AIO-008260 ( Other Grant/Funding Number: Celgene )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AIO-Studien-gGmbH:
NSCLC
Non small cell lung cancer
Additional relevant MeSH terms:
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Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma of Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Paclitaxel
Vinorelbine
Carboplatin
Durvalumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents