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

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ClinicalTrials.gov Identifier: NCT03087708
Recruitment Status : Recruiting
First Posted : March 22, 2017
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

March 16, 2017
March 22, 2017
September 6, 2018
October 13, 2017
April 2019   (Final data collection date for primary outcome measure)
  • Observed accrual rate defined as rate of accrual remaining >= 80% of the expected [ Time Frame: Up to 2 years ]
    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.
  • Proportion of patients alive who continue study drug and complete the health-related quality of life and other forms [ Time Frame: Up to 6 months ]
    The proportion of patients alive at 6 months who continue study drug and complete the health-related quality of life and other forms for at least 6 months will be calculated by arm.
  • Incidence of adverse events as described and graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0 [ Time Frame: Up to 2 years ]
    The frequency of adverse events will be summarized by arm and compared between each treatment arm vs the placebo arm using Fisher's exact test.
  • Observed accrual rate defined as rate of accrual remaining >= 80% of the expected [ Time Frame: Up to 2 years ]
    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.
  • Proportion of patients alive who continue study drug and complete the HRQoL and other forms [ Time Frame: Up to 6 months ]
    The proportion of patients alive at 6 months who continue study drug and complete the HRQoL and other forms for at least 6 months will be calculated by arm.
  • Incidence of adverse events as described and graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, (CTCAE) version 4.0 [ Time Frame: Up to 2 years ]
    The frequency of adverse events will be summarized by arm and compared between each treatment arm vs the placebo arm using Fisher's exact test.
Complete list of historical versions of study NCT03087708 on ClinicalTrials.gov Archive Site
  • Change in trial outcome index [ Time Frame: Baseline to 6 months ]
    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.
  • Change in function subscales [ Time Frame: Baseline to 6 months ]
    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.
  • Change in lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ Time Frame: Baseline to 6 months ]
    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.
  • Patient-reported outcome assessed by Patient-Reported Outcome-Common Terminology Criteria for Adverse Events [ Time Frame: Up to 2 years ]
    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.
  • Patient-reported outcome assessed by a urinary retention Linear Analogue Self-Assessment [ Time Frame: Up to 2 years ]
    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.
  • Opioid-induced constipation rating scale [ Time Frame: Up to 2 years ]
    Opioid-induced constipation rating scale will be summarized by arm. Scores will be compared between treatment arms vs. placebo arm using Wilcoxon test.
  • Level of pain [ Time Frame: Up to 2 years ]
    Pain scores will be summarized by arm. Pain scores will be compared between treatment arms vs. placebo using Wilcoxon test.
  • Analgesic use [ Time Frame: Up to 2 years ]
    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.
  • Unexpected clinical outcomes with chemotherapy [ Time Frame: Up to 2 years ]
    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.
  • 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 ]
    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.
  • Overall survival [ Time Frame: From randomization to death or loss to follow-up, whichever occurs first, assessed up to 2 years ]
    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.
  • Prognostic effect of MOR expression/interaction on health-related quality of life [ Time Frame: Up to 2 years ]
    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.
  • Change in trial outcome index [ Time Frame: Baseline to 6 months ]
    HRQoL scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean standard deviation (SD), median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in HRQoL between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
  • Change in function subscales [ Time Frame: Baseline to 6 months ]
    HRQoL scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean SD, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in HRQoL between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
  • Change in lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ Time Frame: Baseline to 6 months ]
    HRQoL scores at each timepoint and changes in scores between 6 months and baseline will be summarized by mean SD, median (inter-quartile range). Scores will be plotted to explore the pattern over time and to examine differences between treatment arms. Differences in HRQoL between the treatment arms and the placebo arm will be conducted through linear mixed models and growth curve models to account for repeated assessments.
  • Patient-reported outcome (PRO) assessed by PRO-CTCAEs [ Time Frame: Up to 2 years ]
    PRO-CTCAE items will be summarized by arm. PRO-CTCAE response will be compared between the treatment arms vs. placebo arm using a chi-square test or Fisher's exact test as appropriate.
  • PRO assessed by a urinary retention Linear Analogue Self-Assessment (LASA) [ Time Frame: Up to 2 years ]
    LASA items will be summarized by arm. LASA scores will be compared between treatment arms vs. placebo arm using Wilcoxon test.
  • Opioid-induced constipation rating scale (OIC) [ Time Frame: Up to 2 years ]
    OIC rating scale will be summarized by arm. Scores will be compared between treatment arms vs. placebo arm using Wilcoxon test.
  • Level of pain [ Time Frame: Up to 2 years ]
    Pain scores will be summarized by arm. Pain scores will be compared between treatment arms vs. placebo using Wilcoxon test.
  • Analgesic use [ Time Frame: Up to 2 years ]
    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.
  • Unexpected clinical outcomes with chemotherapy [ Time Frame: Up to 2 years ]
    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.
  • PFS 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 ]
    PFS 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 PFS.
  • OS [ Time Frame: From randomization to death or loss to follow-up, whichever occurs first, assessed up to 2 years ]
    OS 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 OS.
  • Prognostic effect of MOR expression/interaction on HRQoL [ Time Frame: Up to 2 years ]
    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.
Not Provided
Not Provided
 
Naloxegol in Treating Patients With Stage IIIB-IV Non-small Cell Lung Cancer
A Randomized, Double-Blind, Placebo-Controlled Pilot Study of an Oral, Selective Peripheral Opioid Receptor Antagonist in Advanced Non-small Cell Lung Cancer (Adenocarcinoma)
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
  • Stage IIIB Lung Adenocarcinoma
  • Stage IIIB Non-Small Cell Lung Cancer
  • Stage IV Lung Adenocarcinoma
  • Stage IV Non-small Cell Lung Cancer
  • Drug: Naloxegol
    Given PO
  • Other: Placebo
    Given PO
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
  • Active Comparator: Group I (lower dose naloxegol, placebo)
    Patients 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.
    Interventions:
    • Drug: Naloxegol
    • Other: Placebo
    • Other: Laboratory Biomarker Analysis
    • Other: Quality-of-Life Assessment
  • Active Comparator: Group II (placebo, higher dose naloxegol)
    Patients 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.
    Interventions:
    • Drug: Naloxegol
    • Other: Placebo
    • Other: Laboratory Biomarker Analysis
    • Other: Quality-of-Life Assessment
  • Placebo Comparator: Group III (placebo)
    Patients 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.
    Interventions:
    • Other: Placebo
    • Other: Laboratory Biomarker Analysis
    • Other: Quality-of-Life Assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
204
Same as current
October 2020
April 2019   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Pankaj Gupta, MD 612-467-4135 pankaj.gupta@va.gov
United States
 
 
NCT03087708
A221504
NCI-2016-01503 ( Registry Identifier: Clinical Trial Reporting Program )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Pankaj Gupta, MD Minneapolis VA Health Care System (University of Minnesota)
Alliance for Clinical Trials in Oncology
September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP