Clinical Trials /

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

NCT03345810

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)
  • Official Title: Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION)

Clinical Trial IDs

  • ORG STUDY ID: AIO-YMO/TRK-0416
  • SECONDARY ID: 2016-003963-20
  • SECONDARY ID: ESR-15-11003
  • NCT ID: NCT03345810

Conditions

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

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Experimental Arm B
VinorelbineExperimental Arm C
GemcitabineExperimental Arm C
nab-PaclitaxelAbraxaneControl Arm A
CarboplatinControl Arm A

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Control Arm AActive ComparatorFrail or elderly patients with metastatic NSCLC; CARG- Score ≤ 3 Carboplatin (AUC 5.0; D1) + nab-Paclitaxe (100mg/m2 D1,D8) Q3W
  • nab-Paclitaxel
  • Carboplatin
Experimental Arm BExperimentalFrail or elderly patients with metastatic NSCLC; CARG- Score ≤ 3 Induction:Carboplatin (AUC 5.0; D1) + nab-Paclitaxe (100mg/m2) D1,D8; Q3W [2 cyc] followed by durvalumab (1125 mg; Q3W) [ 2 cyc] Maintenance:durvalumab (1500 mg) Q4W
  • Durvalumab
  • nab-Paclitaxel
  • Carboplatin
Experimental Arm CExperimentalFrail 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)
  • Durvalumab
  • Vinorelbine
  • Gemcitabine
Control Arm DActive ComparatorFrail or elderly patients with metastatic NSCLC; CARG- Score > 3 Vinorelbine (30 mg/m2; D1+D8) Q3W or Gemcitabine (1000 mg/m2; D1+D8) Q3W
  • Vinorelbine
  • Gemcitabine

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].
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of treatment related Grade III/IV adverse events (CTCAE V4.03)
Time Frame:through study completion, an average of 24 months
Safety Issue:
Description: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

Measure:PFS
Time Frame:approx. 24 months
Safety Issue:
Description:Progression Free Survival
Measure:ORR using assessment according to RECIST 1.1
Time Frame:approx. 24 months
Safety Issue:
Description:Response Evaluation Criteria In Solid Tumors (RECIST)
Measure:OS
Time Frame:approx. 60 months
Safety Issue:
Description:Overall Survival
Measure:Adverse Events /Serious Adverse Events
Time Frame:approx. 48 months
Safety Issue:
Description:Adverse Events: Type, incidence, and severity according to NCI CTCAE version 4.03
Measure:Health related Quality of Life (HR-QoL)
Time Frame:approx. 60 months
Safety Issue:
Description:as determined with FACT-L (Functional Assessment of Cancer Therapy - Lung)
Measure:Geriatric assessment
Time Frame:approx. 60 months
Safety Issue:
Description:G8-questionnaire
Measure:Geriatric assessment
Time Frame:approx. 60 months
Safety Issue:
Description:Timed up & go (test of basic functional mobility)
Measure:Geriatric assessment
Time Frame:approx. 60 months
Safety Issue:
Description:6MWT (6 minutes walk test)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AIO-Studien-gGmbH

Trial Keywords

  • NSCLC
  • Non small cell lung cancer

Last Updated

January 8, 2018