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Testing the Effects of MK-3475 (Pembrolizumab) With or Without the Usual Chemotherapy Treatment for Patients 70 Years of Age and Older With Advanced Non-small Cell Lung Cancer

NCT04533451

Description:

This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Testing the Effects of MK-3475 (Pembrolizumab) With or Without the Usual Chemotherapy Treatment for Patients 70 Years of Age and Older With Advanced Non-small Cell Lung Cancer
  • Official Title: Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice)

Clinical Trial IDs

  • ORG STUDY ID: A171901
  • SECONDARY ID: NCI-2020-00544
  • SECONDARY ID: UG1CA189823
  • NCT ID: NCT04533451

Conditions

  • Metastatic Lung Adenocarcinoma
  • Metastatic Lung Non-Small Cell Carcinoma
  • Recurrent Lung Adenocarcinoma
  • Recurrent Lung Non-Small Cell Carcinoma
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
PembrolizumabGroup A (pembrolizumab)
PemetrexedGroup B (pembrolizumab, pemetrexed, carboplatin)
CarboplatinGroup B (pembrolizumab, pemetrexed, carboplatin)

Purpose

This trial studies the side effects of pembrolizumab with or without chemotherapy in treating patients with stage IV non-small cell lung cancer that has come back (recurrent) and has spread to other places in the body (advanced). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as pemetrexed and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the tumor in older patients with non-small cell lung cancer.

Detailed Description

      The primary and secondary objectives of the study:

      PRIMARY OBJECTIVE:

      I. To estimate the adverse event profile of MK-3475 (pembrolizumab) in non-small cell lung
      cancer patients who are age 70 years of age or older and who are treated with MK-3475
      (pembrolizumab) +/- chemotherapy in a first-line setting.

      SECONDARY OBJECTIVES:

      I. To estimate overall survival. II. To describe patient quality of life during the treatment
      using the Linear Analogue Self-Assessment (LASA) questionnaire.

      III. To explore whether Comprehensive Geriatric Assessment (CGA) -derived risk score is able
      to predict rates of severe adverse events in older cancer patients who receive MK-3475
      (pembrolizumab) or MK-3475 (pembrolizumab) + chemotherapy.

      OUTLINE: Patients are assigned to 1 of 2 groups.

      GROUP A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      GROUP B: Patients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes,
      and carboplatin IV per institutional guidelines on day 1. Cycles repeat every 21 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up annually for up to 5 years
      after registration.
    

Trial Arms

NameTypeDescriptionInterventions
Group A (pembrolizumab)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
Group B (pembrolizumab, pemetrexed, carboplatin)ExperimentalPatients receive pembrolizumab IV over 30 minutes, pemetrexed IV over 10 minutes, and carboplatin IV per institutional guidelines on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • Pembrolizumab
  • Pemetrexed
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Documentation of Disease: Histologic or cytologic diagnosis of non-small cell lung
             cancer (adenocarcinoma). Stage IV or recurrent metastatic non-small cell lung cancer.
             No planned initiation of definitive (potentially curative) concurrent chemo-radiation

          -  Planning to begin MK-3475 (pembrolizumab) treatment within 14 days of registration,
             with or without combination chemotherapy. Treating physician considers pembrolizumab
             as appropriate and plans to proceed with one of the following treatment schedules:

               -  MK-3475 (pembrolizumab) 200 mg IV flat dose every 21 days or 400 mg IV every 42
                  days.

               -  MK-3475 (pembrolizumab) 200 mg IV or 400 mg IV + carboplatin area under the curve
                  (AUC) = 5 + pemetrexed 500 mg/m^2 (20% chemotherapy dose reduction is permitted
                  per the discretion of the treating physician)

          -  Patients will be ineligible if they have an autoimmune disorder, are post-organ
             transplantation, or are receiving ongoing immunosuppression treatment

          -  Prior adjuvant therapy is allowed and must have been completed at least 6 months prior
             to registration

          -  No planned radiation or other cancer treatment in the 3 months following registration

          -  No untreated brain metastases. Patients must be off corticosteroids and asymptomatic
             at registration

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (1.5 x 10^9/L)

          -  Platelet count: >= 100,000/mm^3 (100 x 10^9/L)

          -  Creatinine >= 30 mL/min* for patients enrolled to pembrolizumab alone and > 45 mL/min
             for patients enrolled to chemotherapy + pembrolizumab

             * Calculated using the Cockcroft-Gault formula

          -  Total serum bilirubin =< 1.5 upper limit of normal (ULN) (< 3 ULN if Gilbert's
             disease)

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x ULN (=<
             5.0 x ULN if liver metastases present)

          -  Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN if bone or liver metastases present)
             Language: Patients must be able to speak and comprehend English in order to complete
             the mandatory patient-completed measures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of grade 3 or worse adverse events post registration
Time Frame:Up to 7 days of last day of treatment
Safety Issue:
Description:Assessed by National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0. The proportion of patients experience grade 3 or worse adverse events (AEs) will be summarized by frequency and percentage along with a 95% confidence interval (CI) separately by type of therapy (monotherapy or combination therapy) as well as combining the two cohorts. All other individual AEs will be analyzed in an exploratory and hypothesis generating manner; including and not limited to multi-variate logistic regression models considering the baseline demographics and the presence/absence of the AE.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:From study registration to death or the last follow-up whichever occurs first, assessed up to 5 years
Safety Issue:
Description:Will be summarized using the Kaplan-Meier estimator, separately by monotherapy or combination therapy as well as by the combined cohort.
Measure:Quality of life (QOL): Linear Analogue Self-Assessment [LASA] questionnaire
Time Frame:Up to 5 years
Safety Issue:
Description:The overall quality of life score (the first question of the Linear Analogue Self-Assessment [LASA] questionnaire) at each time point as well as change from baseline will be summarized by mean (standard deviation), median (range) along with a longitudinal plot. The median quality of life (QOL) change from baseline along with a 95% confidence interval (CI) will be estimated using the Hodges-Lehmann method. The overall quality of life score will be measured on a scale from 0-10, with higher being better.
Measure:Comprehensive geriatric assessment risk score
Time Frame:At baseline
Safety Issue:
Description:The geriatric risk score, measured as low, medium, or high, will be summarized in a 3X2 frequency table with adverse events.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Alliance for Clinical Trials in Oncology

Last Updated

October 15, 2020