Clinical Trials /

1st Line Durvalumab in PS 2 NSCLC Patients

NCT03620669

Description:

The aim of the trial is to assess efficacy and safety of the treatment with durvalumab in PS 2 patients with treatment-naïve, locally advanced or metastatic, PD-L1 positive NSCLC who are considered unsuitable for combination platinum-containing therapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

    <li>Brief Title: 1st Line Durvalumab in PS 2 NSCLC Patientsli><li>Official Title: First Line Durvalumab in Patients With PD-L1 Positive, Advanced NSCLC With Performance Status 2 Unsuitable for Combination Chemotherapy. A Multicenter, Single-arm Phase II Trialli>

Clinical Trial IDs

    <li>ORG STUDY ID: SAKK 19/17li><li>NCT ID: NCT03620669li>

Conditions

    <li>NSCLC Stage IVli><li>NSCLC Stage IIIBli>

Interventions

<td>Durvalumabtd><td>MEDI4736td><td>Durvalumabtd>
DrugSynonymsArms

Purpose

The aim of the trial is to assess efficacy and safety of the treatment with durvalumab in PS 2 patients with treatment-naïve, locally advanced or metastatic, PD-L1 positive NSCLC who are considered unsuitable for combination platinum-containing therapy.

Detailed Description

      Lung cancer is the leading cause of cancer deaths. An estimated 30 to 40% of patients
      diagnosed with NSCLC have a poor Performance status (PS) defined as a score of 2 or higher on
      the ECOG scale. PS 2 patients are often underrepresented in clinical trials despite
      representing a very frequent and important subgroup.

      Platinum-based (preferably carboplatin) doublets should be considered as standard of care in
      eligible PS 2 patients. However the toxicity profile of platinum-based doublets remains a
      concern. Single-agent chemotherapy represents an alternative treatment option for the PS 2
      patients considered unsuitable for platinum doublet chemotherapy but its efficacy is limited
      and the outcome poor.

      Given the superiority of the anti-PD-1 antibody pembrolizumab versus standard chemotherapy as
      first line therapy in a PD-L1 positive NSCLC population, it now became the standard
      treatment. The PS of patients enrolled in these trials were PS 0 or 1, making the benefit of
      PD-L1 antibodies in PS 2 patients unclear. A retrospective real-life data analysis of
      nivolumab in metastatic NSCLC revealed similar treatment-related AE between patients with a
      PS of 0 or 1 with those having a PS of 2, confirming good treatment tolerability in poor PS
      patients.

      The overall favorable toxicity profile of durvalumab and the absence of robust efficacy data
      of checkpoint inhibitors in first line treatment of patients with PD-L1 positive NSCLC with a
      PS of 2, encourage to investigate its activity in this cohort of patients when considered
      unsuitable for platinum doublet chemotherapy.

      Finally, this trial aims to prolong overall survival by treating this cohort of frail
      patients with durvalumab, compared to historical controls, treated with single agent
      chemotherapy.
    

Trial Arms

<td>Durvalumabtd><td>Experimentaltd><td>Durvalumab until progression or unacceptable toxicitytd><td>
    <li>Durvalumabli>
td>
NameTypeDescriptionInterventions

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent according to Swiss law and ICH/GCP regulations before
             registration and prior to any trial specific procedures

          -  Histologically confirmed NSCLC, advanced or recurrent disease (stage IIIB or IV).
             Cytology could be accepted if histology is not possible

          -  PD-L1 expression of ≥ 25% of the tumor cells by local testing (Ventana SP142 excluded)

          -  No sensitizing EGFR mutation (L858R or exon 19 deletions), ALK fusion oncogene or
             rearrangements of the ROS1 gene detected

          -  Patient unsuitable for platinum-containing combination chemotherapy according to
             investigator or due to patient preference

          -  WHO PS of 2

          -  Age ≥ 18 years

          -  Baseline QoL forms and GA questionnaires have been completed

          -  Bone marrow function: hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 x 109/L, platelet
             count ≥ 100 x 109/L

          -  Hepatic function: bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤
             3.0 x ULN); patients without liver metastases: AST and ALT ≤ 2.5 x ULN, patients with
             documented liver metastases: AST and ALT ≤ 5 x ULN

          -  Renal function: estimated glomerular filtration rate (eGFR)> 30 mL/min/1.73m²
             (according to CKD-EPI formula)

          -  Measurable or evaluable disease (by RECIST v1.1)

          -  Patients with asymptomatic untreated CNS metastases are eligible, provided they meet
             the following:

               -  ≤ 5 CNS lesions with a maximum diameter of one lesion of 10 mm

               -  Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons,
                  cerebellum, medulla, or spinal cord)

               -  No evidence of progression at registration compared to the latest brain imaging

               -  No ongoing requirement for corticosteroids as therapy for CNS disease

          -  Patients with symptomatic treated CNS metastases are eligible, provided they meet the
             following:

               -  No ongoing requirement for corticosteroids as therapy for CNS disease;
                  anticonvulsants at a stable dose allowed

               -  No stereotactic radiation or whole-brain radiation within 7 days prior to
                  registration

               -  No evidence of progression at registration, after completion of CNS-directed
                  therapy

          -  Tumor tissue available for central PD-L1 assessment and translational research
             (preferably histology but cytology could be allowed if histology is not possible). In
             case of scarce tumor material, a rebiopsy, if clinically possible, is encouraged

          -  Women with child-bearing potential are using effective contraception, are not pregnant
             or lactating and agree not to become pregnant during trial treatment and during the 3
             months thereafter. A negative pregnancy test before inclusion into the trial is
             required for all women with child-bearing potential

          -  Men agree not to father a child during trial treatment and during 3 months thereafter

          -  Body weight > 30kg.

        Exclusion criteria:

        Any potential patient who meets any of the following criteria has to be excluded from
        entering the trial.

          -  History of hematologic or primary solid tumor malignancy, unless in remission for at
             least 3 years before registration with the exception of pT1-2 prostate cancer Gleason
             score <6, adequately treated cervical carcinoma in situ or localized non-melanoma skin
             cancer

          -  Prior adjuvant systemic anti-cancer treatment within 6 months before registration

          -  Prior systemic treatment for metastatic NSCLC

          -  Prior treatment with a PD-1 or PD-L1 inhibitor

          -  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 (i.e. which must not exceed 10 mg/day
             of prednisone or an equivalent corticosteroid)

          -  Concomitant drugs contraindicated for use with durvalumab such as corticosteroids,
             methotrexate, azathioprine and tumor necrosis factor (TNF)-α blockers

          -  Concurrent treatment with other experimental drugs or other anticancer therapy,
             treatment in a clinical trial within 28 days prior to registration

          -  Major surgical procedure within 14 days prior to registration

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion:

               -  Patients with vitiligo or alopecia

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               -  Any chronic skin condition that does not require systemic therapy

               -  Patients without active disease in the last 5 years may be included but only
                  after consultation with the coordinating investigator

               -  Patients with celiac disease controlled by diet alone

          -  Uncontrolled diabetes mellitus

          -  Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
             Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
             intravenous (iv) antimicrobial treatment

          -  Known history of tuberculosis

          -  Known history of primary immunodeficiency

          -  Known history of allogeneic organ transplant

          -  Receipt of live attenuated vaccine within 28 days prior to registration

          -  Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
             IV; unstable angina pectoris, history of myocardial infarction within the last six
             months, serious arrhythmias requiring medication (with exception of atrial
             fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation,
             uncontrolled hypertension

          -  Any other serious underlying medical, psychiatric, psychological, familial or
             geographical condition, which in the judgment of the investigator may interfere with
             the planned staging, treatment and follow-up, affect patient compliance or place the
             patient at high risk from treatment-related complications.
      
<td>Maximum Eligible Age:td><td>N/Atd><td>Minimum Eligible Age:td><td>18 Yearstd><td>Eligible Gender:td><td>Alltd><td>Healthy Volunteers:td><td>Notd>

Primary Outcome Measures

<td>Measure:td><td>Overall survival (OS) at 6 monthstd><td>Time Frame:td><td>At 6 months after registrationtd><td>Safety Issue:td><td/><td>Description:td><td>OS at 6 months is defined as being alive at 6 months after registration.td>

Secondary Outcome Measures

<td>Measure:td><td>Objective response (OR) according to RECIST 1.1td><td>Time Frame:td><td>At trial treatment discontinuation or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>OR is defined as any complete response (CR) or partial response (PR) according to RECIST 1.1 criteria achieved during trial treatment.td>
<td>Measure:td><td>Objective response according to iRECIST (iOR)td><td>Time Frame:td><td>At trial treatment discontinuation or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>iOR is defined as any complete response (CR/iCR) or partial response (PR/iPR) according to RECIST1.1 or iRECIST criteria achieved during trial treatment.td>
<td>Measure:td><td>Duration of response (DoR) according to RECIST 1.1td><td>Time Frame:td><td>Atdisease progression according to RECIST 1.1 criteria or death due to disease progression or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>DoR is defined as the time from the first documentation of OR until disease progression according to RECIST 1.1 criteria or death due to disease progression, whichever occurs first.td>
<td>Measure:td><td>Duration of response according to iRECIST (iDoR)td><td>Time Frame:td><td>Atdisease progression according to iRECIST criteria (iPD) or death due to disease progression or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>iDoR is defined as the time from the first documentation of iOR until disease progression according to iRECIST criteria (iPD) or death due to disease progression.td>
<td>Measure:td><td>Progression-free survival (PFS) according to RECIST 1.1td><td>Time Frame:td><td>Atdisease progression according to RECIST v1.1 criteria or death due to any cause or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>PFS is defined as the time from registration until disease progression according to RECIST v1.1 criteria or death due to any cause, whichever occurs first.td>
<td>Measure:td><td>Progression-free survival according to iRECIST (iPFS)td><td>Time Frame:td><td>Atdisease progression according to iRECIST criteria (iPD) or death due to any reason or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>iPFS is defined as the time from registration until disease progression according to iRECIST criteria (iPD) or death due to any reason, whichever occurs first. iPD is defined as the time point of first iUPD without subsequent iSD, iPR or iCR before trial treatment discontinuation. Patients not experiencing an event at the time of the analysis, as well as patients starting a subsequent anticancer treatment in the absence of an event, will be censored at the date of their last available tumor assessment showing no evidence of iPD before starting a subsequent anticancer treatment, if any.td>
<td>Measure:td><td>Overall survival (OS)td><td>Time Frame:td><td>At death of the patient or the latest 5 years after last patient discontinued trial treatmenttd><td>Safety Issue:td><td/><td>Description:td><td>OS is defined as the time from registration until death due to any causetd>
<td>Measure:td><td>Adverse events (AEs)td><td>Time Frame:td><td>From registration until 28 days after last trial treatment dosetd><td>Safety Issue:td><td/><td>Description:td><td>All AEs will be assessed according to NCI CTCAE v5.0td>
<td>Measure:td><td>Quality of life (QoL): Core 30 (QLQ-C30)td><td>Time Frame:td><td>From registration until trial treatment discontinuation or the latest 1 year after registrationtd><td>Safety Issue:td><td/><td>Description:td><td>QoL is measured by the Questionnaire Core 30 (QLQ-C30) including the complementary Lung Cancer Module (QLQ-LC13)td>
<td>Measure:td><td>Geriatric assessment (GA)td><td>Time Frame:td><td>At baselinetd><td>Safety Issue:td><td/><td>Description:td><td>Screening instrument (G8)td>
<td>Measure:td><td>Geriatric assessment (GA)td><td>Time Frame:td><td>At baselinetd><td>Safety Issue:td><td/><td>Description:td><td>Assessment with IADLtd>
<td>Measure:td><td>Geriatric assessment (GA)td><td>Time Frame:td><td>At baselinetd><td>Safety Issue:td><td/><td>Description:td><td>Comorbidities assessment with CCItd>

Details

<td>Phase:td><td>Phase 2td><td>Primary Purpose:td><td>Interventionaltd><td>Overall Status:td><td>Not yet recruitingtd><td>Lead Sponsor:td><td>Swiss Group for Clinical Cancer Researchtd>

Trial Keywords

    <li>Lung cancerli><li>Durvalumabli><li>PD-L1li><li>NSCLCli><li>Phase IIli><li>PS 2li>

Last Updated

<p/>