Clinical Trials /

Pembrolizumab in Elderly Patients With Advanced Lung Cancer

NCT03293680

Description:

This is a multi-center phase II trial of intravenous (IV) Pembrolizumab MK-3475 in subjects older than 70 years with advanced Non-small cell Lung Cancer (NSCLC) expressing Programmed death-ligand 1 (PD-L1). 82 patients will be enrolled in this trial to examine the efficacy, the impact on geriatric assessments, the quality of life and the self-reported outcomes.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Elderly Patients With Advanced Lung Cancer
  • Official Title: Survival, Quality of Life and Self-reported Outcomes of Elderly Patients With Advanced Non-small Cell Lung Cancer Treated With Pembrolizumab (MK-3475) in the First Line Setting

Clinical Trial IDs

  • ORG STUDY ID: GECP 16/06_PEBEL
  • NCT ID: NCT03293680

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab Arm

Purpose

This is a multi-center phase II trial of intravenous (IV) Pembrolizumab MK-3475 in subjects older than 70 years with advanced Non-small cell Lung Cancer (NSCLC) expressing Programmed death-ligand 1 (PD-L1). 82 patients will be enrolled in this trial to examine the efficacy, the impact on geriatric assessments, the quality of life and the self-reported outcomes.

Detailed Description

      Subjects will receive MK-3475 at a fixed dose of 200 mg every 3 weeks (Q3W) (Figure 1).
      Subjects will be evaluated every 9 weeks (63 ± 7 days) with radiographic imaging to assess
      response to treatment. QoL and Self-reported Health Questionnaires, as well as geriatric
      follow-up will be performed at the same intervals. Investigators will make all
      treatment-based decisions using immune-related Response Criteria (irRC). However, for
      determination of overall response rate (ORR) and progression-free survival (PFS), the
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be used. Adverse events will
      be monitored throughout the trial and graded in severity according to the guidelines outlined
      in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment with
      MK-3475 will continue until two years of therapy have been administered, documented disease
      progression, unacceptable adverse event(s), intercurrent illness that prevents further
      administration of treatment, investigator's decision to withdraw the subject, subject
      withdraws consent, noncompliance with trial treatment or procedure requirements, or
      administrative reasons.

      After the end of treatment, each subject will be followed for a minimum of 30 days for
      adverse event monitoring (serious adverse events will be collected for up to 90 days after
      the end of treatment unless the subject starts a new anticancer therapy between days 31 and
      90). Subjects will have post-treatment follow-up for disease status, including initiating a
      non-study cancer treatment and experiencing disease progression, until death, withdrawing
      consent, or becoming lost to follow-up.

      Participation in this trial will be dependent upon supplying tumor tissue from a newly
      obtained formalin-fixed specimen from locations not radiated prior to biopsy. The specimen
      will be evaluated at a central laboratory facility for expression status of Programmed
      death-ligand 1(PD-L1) in a prospective manner. Only subjects whose tumors express Programmed
      death-ligand 1(PD-L1) as determined by the central laboratory facility will be eligible for
      inclusion in this study.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab ArmExperimental1 group, Pembrolizumab (MK-3475) 200 mg, every 3 weeks
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with histological or cytological documented stage III B or IV squamous and
             non-squamous non-small-cell lung cancer previously untreated.

          2. Epidermal Growth Factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) have to
             be wild-type.

          3. The subject must be willing and able to provide written informed consent/assent for
             the trial.

          4. Patients must be aged more than 70 years, on day of signing informed consent.

          5. Measurable disease (at least 1 lesion) based on RECIST criteria v1.1. Patients will
             not be eligible if this lesion was irradiated before inclusion.

          6. Be willing to provide tissue from a newly obtained core or excision biopsy of a tumor
             lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior
             to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot
             be provided (e.g. inaccessible or subject safety concern) may submit an archived
             specimen only upon agreement from the Sponsor.

          7. PD-L1 expression ≥ 1%

          8. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group
             Performance Scale.

          9. Screening laboratory values must meet the following criteria (Table 1, see protocol),
             all screening laboratory tests should be performed within 8 days of treatment
             initiation.

         10. Male subjects of childbearing potential must agree to use an adequate method of
             contraception, starting with the first dose of study therapy through 120 days after
             the last dose of study therapy.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose
             over 10 mg of prednisone or equivalent, or any other form of immunosuppressive therapy
             within 7 days prior to the first dose of trial treatment.

          3. Has a known history of active Tuberculosis Bacillus

          4. Hypersensitivity to Pembrolizumab or any of its excipients.

          5. Has had any prior anti-cancer therapy for his or her metastatic NSCLC. In the case of
             patients who have progressed to a metastatic stage after having been treated for early
             stage NSCLC, chemotherapy or radiation therapy as part of this previous treatment is
             allowed, provided they have been completed more than three months ago. Patients who
             received adjuvant or neoadjuvant treatment or both for early stages will be eligible
             for this trial. All adverse events related to these previous treatments must have
             recovered (i.e., ≤ Grade 1 or at baseline).

          6. Has had any previous malignancy (except non melanoma skin cancer, and cancer in situ
             of: bladder, gastric, colon, cervical/dysplasia, melanoma, breast), unless a complete
             remission was achieved at least 2 years prior to study entry and no additional therapy
             is required or anticipated to be required during the study period.

          7. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate if they
             are stable (without evidence of progression by imaging for at least four weeks prior
             to the first dose of trial treatment and any neurologic symptoms have returned to
             baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids at a dose over 10 mg of prednisone or equivalent, for at least 7 days prior
             to trial treatment. This exception does not include carcinomatous meningitis which is
             excluded regardless of clinical stability.

          8. Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (eg., thyroxin, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
             form of systemic treatment.

          9. Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

         10. Has an active infection requiring systemic therapy.

         11. Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

         12. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         13. Has any geriatric exclusion criteria:

               -  advanced dementia (GDS ranking >6)

               -  moderate or severe functional dependence (Barthel Index < 35)

               -  Life expectancy less than one year, due to co-morbidities other than lung cancer.

         14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C
             Virus RNA [qualitative] is detected).

         16. Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

         17. Evidence of interstitial lung disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy of the treatment at 12 months (overall survival of the patients)
Time Frame:From the date of inclusion of the first patient to 12 months after this date
Safety Issue:
Description:To evaluate the overall survival of the patients included at one year

Secondary Outcome Measures

Measure:Changes in health-related quality of life with Lung Cancer Symptom Scale
Time Frame:From the first dose until 12 months (time of the last dose of treatment)
Safety Issue:
Description:To evaluate changes in health-related quality of life in responder and non-responder patients older than 70 years with advanced non-small cell lung cancer
Measure:Impact on cognitive assessments measured with Edmonton scale
Time Frame:From the first dose until the last dose of treatment (12 months later)
Safety Issue:
Description:To evaluate the impact on cognitive geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.
Measure:Impact on functional assessments measured with Barthel scale
Time Frame:From the first dose until the last dose of treatment (12 months later)
Safety Issue:
Description:To evaluate the impact on functional geriatric assessments of patients older than 70 years with advanced non-small cell lung cancer.
Measure:Progression-free Survival (PFS)
Time Frame:From the inclusion date in the study until first progression (at 9 months approximately) documented according to RECIST criteria
Safety Issue:
Description:To describe Progression-free Survival (PFS), according to RECIST criteria v. 1.1 of the first-line treatment with pembrolizumab (MK-3475) in elderly patients with advanced NSCLC
Measure:Median Overall Survival rate at 2 years.
Time Frame:From the date of inclusion of the first patient to 24 months after this date
Safety Issue:
Description:To evaluate the overall survival of the patients included at two years
Measure:Safety (Adverse events) and tolerability (quantity of infusion and adverse events related with them) profile
Time Frame:From the date of the first infusion of medication until 90 days after the last dose
Safety Issue:
Description:To describe the safety and tolerability profile of first-line pembrolizumab (MK-3475) in previously untreated elderly patients

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Spanish Lung Cancer Group

Last Updated

March 13, 2018