Clinical Trials /

Naloxegol in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer

NCT03087708

Description:

This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Naloxegol in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
  • Official Title: A Randomized, Double-Blind, Placebo-Controlled Pilot Study of an Oral, Selective Peripheral Opioid Receptor Antagonist in Advanced Non-small Cell Lung Cancer (Adenocarcinoma)

Clinical Trial IDs

  • ORG STUDY ID: A221504
  • SECONDARY ID: NCI-2016-01503
  • NCT ID: NCT03087708

Conditions

  • Stage IIIB Lung Adenocarcinoma
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Lung Adenocarcinoma
  • Stage IV Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
NaloxegolGroup I (lower dose naloxegol, placebo)

Purpose

This randomized pilot clinical trial studies the side effects and best dose of naloxegol and to see how well it works in treating patients with stage IIIB-IV non-small cell lung cancer. Naloxegol may relieve some of the side effects of opioid pain medication and fight off future growth in the cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine feasibility and safety of long-term administration of two doses of a
      peripheral opioid receptor antagonist in patients with advanced non-small cell lung cancer
      (NSCLC) receiving first-line pemetrexed-based chemotherapy.

      SECONDARY OBJECTIVES:

      I. To explore whether patients randomized to one or both of the two study drug arms have less
      decline in health-related quality of life (HRQoL) than patients randomized to placebo.

      II. To estimate the difference in the pain levels and opioid/non-opioid analgesic
      requirements between patients receiving naloxegol or placebo.

      III. To estimate the difference in the adverse peripheral effects of opioids (e.g.
      constipation, nausea/emesis, dry mouth and urinary retention) between patients receiving
      naloxegol or placebo.

      IV. To explore whether there is a signal that naloxegol may be associated with longer
      progression-free survival (PFS) and overall survival (OS).

      V. To evaluate the difference in discontinuation rate of chemotherapy due to adverse events
      (AEs) and deaths attributable to chemotherapy.

      After completion of study treatment, patients are followed up every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (lower dose naloxegol, placebo)Active ComparatorPatients receive lower dose naloxegol PO QD and placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
  • Naloxegol
Group II (placebo, higher dose naloxegol)Active ComparatorPatients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.
  • Naloxegol
Group III (placebo)Placebo ComparatorPatients receive placebo PO QD. Courses repeat every 3 weeks in year 1 and then every 3 months in year 2 in the absence of unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Advanced (stage IIIB or IV) lung adenocarcinoma diagnosed by biopsy of the primary or
                 metastatic site (American Joint Committee on Cancer 7.0)
    
              -  No known presence of known EGFR or EML4-ALK driver mutations in the tumor
    
              -  Initiation of first-line chemotherapy with a platinum-pemetrexed-based regimen within
                 14 days of registration or planning to initiate within 14 days after registration; no
                 planned initiation of definitive (potentially curative) concurrent chemo-radiation
    
              -  No prior systemic therapy for advanced NSCLC, including chemotherapy, targeted therapy
                 or immunotherapy; prior palliative radiation permitted; prior adjuvant
                 chemotherapy/radiation is permitted
    
              -  No past or current use of mixed opioid agonist/opioid antagonists or other opioid
                 antagonists
    
              -  No methadone within 4 weeks prior to registration
    
              -  Patients must have used opioid medication(s) for pain at some time in the 4 weeks
                 prior to registration; current use of opioids (at the time of registration) and/or
                 later during the course of the study is permitted but not required
    
              -  Expected survival > 3 months
    
              -  No concurrently active second invasive malignancies except non-melanoma skin cancer
    
              -  No history of gastrointestinal obstruction, or conditions that increase the risk of
                 gastrointestinal obstruction, perforation, bleeding or impairment of the
                 gastrointestinal wall; no abdominal surgery within 60 days of registration
    
              -  No acute gastrointestinal conditions, such as: obstruction, fecal impaction,
                 obstipation, acute surgical abdomen, ongoing need for manual maneuvers to induce bowel
                 movements (such as digital evacuation)
    
              -  No conditions that may compromise blood-brain barrier permeability (e.g., multiple
                 sclerosis, recent brain trauma, Alzheimer's disease, or uncontrolled seizures)
    
                   -  No symptomatic and untreated brain metastases; patients will be eligible for
                      study if radiation therapy for brain metastases was completed at least 7 days
                      prior to registration
    
                   -  Patients having received stereotactic radiation will be eligible if the radiation
                      was completed at least 7 days prior to registration
    
                   -  Patients having undergone surgical resection of brain metastases will be eligible
                      after they have healed and recovered from the surgical intervention sufficiently
                      to start systemic treatment for NSCLC, as determined by a neurosurgeon
    
                   -  No known leptomeningeal carcinomatosis
    
              -  No history of myocardial infarction =< 6 months prior to registration; no current
                 symptomatic congestive heart failure, uncontrolled angina, or uncontrolled cardiac
                 arrhythmias
    
              -  No severe hepatic impairment (Child-Pugh class C) or acute liver disease
    
              -  No known serious or severe hypersensitivity reaction to naloxegol or any of its
                 excipients
    
              -  No concurrent use of moderate/strong CYP3A4 inhibitors, or strong CYP3A4 inducers
    
              -  Not pregnant and not nursing; for women of childbearing potential only, a negative
                 pregnancy test done =< 7 days prior to registration is required; a female of
                 childbearing potential is a sexually mature female who: 1) has not undergone a
                 hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
                 for at least 12 consecutive months (i.e., has had menses at any time in the preceding
                 12 consecutive months)
    
              -  Age ≥ 18 years
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2
    
              -  Absolute neutrophil count (ANC) >= 1,500/mm^3
    
              -  Platelet count >= 100,000/mm^3
    
              -  Calculated (calc.) creatinine clearance >= 60 mL/min calculated using the
                 Cockcroft-Gault formula
    
              -  Total bilirubin =< 1.2 x upper limit of normal (ULN) unless due to Gilbert's disease
    
              -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
                 limit of normal (ULN)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Observed accrual rate defined as rate of accrual remaining >= 80% of the expected
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Calculated as the total number of patients accrued to the study over two years divided by 184, the total expected accrual of patients evaluable for the primary endpoint.

    Secondary Outcome Measures

    Measure:Change in trial outcome index
    Time Frame:Baseline to 6 months
    Safety Issue:
    Description:Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
    Measure:Change in function subscales
    Time Frame:Baseline to 6 months
    Safety Issue:
    Description:Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
    Measure:Change in lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung
    Time Frame:Baseline to 6 months
    Safety Issue:
    Description:Health-related quality of life scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in health-related quality of life between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
    Measure:Patient-reported outcome assessed by Patient-Reported Outcome-Common Terminology Criteria for Adverse Events
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Patient-Reported Outcome-Common Terminology Criteria for Adverse Events items will be summarized by arm. Patient-Reported Outcome-Common Terminology Criteria for Adverse Events response will be compared between the treatment arms vs. placebo arm using a chi-square test or Fisher's exact test as appropriate.
    Measure:Patient-reported outcome assessed by a urinary retention Linear Analogue Self-Assessment
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Linear Analogue Self-Assessment items will be summarized by arm. Linear Analogue Self-Assessment scores will be compared between treatment arms versus placebo arm using Wilcoxon test.
    Measure:Opioid-induced constipation rating scale
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Opioid-induced constipation rating scale will be summarized by arm. Scores will be compared between treatment arms vs. placebo arm using Wilcoxon test.
    Measure:Level of pain
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Pain scores will be summarized by arm. Pain scores will be compared between treatment arms vs. placebo using Wilcoxon test.
    Measure:Analgesic use
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Analgesic use will be summarized by arm. Frequencies of analgesic used will be compared using chi-square test or Fisher's exact test, as appropriate.
    Measure:Unexpected clinical outcomes with chemotherapy
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Frequency of discontinuation of chemotherapy will be summarized by arm and compared between each treatment arm vs the placebo arm using Fisher's exact test.
    Measure:Progression-free survival assessed by using the standard Response Evaluation Criteria in Solid Tumors 1.1 criteria
    Time Frame:From randomization to disease progression/relapse, death, or loss to follow-up, whichever occurs first, assessed up to 2 years
    Safety Issue:
    Description:Progression-free survival probabilities will be estimated by arm using the Kaplan-Meier estimator. In an exploratory manner, a Cox proportional hazards model will be used to determine the effect of naloxegol on progression-free survival.
    Measure:Overall survival
    Time Frame:From randomization to death or loss to follow-up, whichever occurs first, assessed up to 2 years
    Safety Issue:
    Description:Overall survival probabilities will be estimated by arm using the Kaplan-Meier estimator. In an exploratory manner, a Cox proportional hazards model will be used to determine the effect of naloxegol on overall survival.
    Measure:Prognostic effect of MOR expression/interaction on health-related quality of life
    Time Frame:Up to 2 years
    Safety Issue:
    Description:MOR expression and activation will be included as a covariate in the linear mixed model, an interaction between MOR expression/activation and treatment will be evaluated.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Alliance for Clinical Trials in Oncology

    Last Updated

    October 16, 2017