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Trial record 43 of 207 for:    Oral Cancer | Recruiting Studies | NIH

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

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stage IIIB Lung Adenocarcinoma Stage IIIB Non-Small Cell Lung Cancer Stage IV Lung Adenocarcinoma Stage IV Non-small Cell Lung Cancer Drug: Naloxegol Other: Placebo Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
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)
Actual Study Start Date : October 13, 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Naloxegol

Arm Intervention/treatment
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.
Drug: Naloxegol
Given PO

Other: Placebo
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies

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.
Drug: Naloxegol
Given PO

Other: Placebo
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies

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.
Other: Placebo
Given PO

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03087708


Contacts
Contact: Pankaj Gupta, MD 612-467-4135 pankaj.gupta@va.gov

  Show 473 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Pankaj Gupta, MD Minneapolis VA Health Care System (University of Minnesota)

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT03087708     History of Changes
Other Study ID Numbers: A221504
NCI-2016-01503 ( Registry Identifier: Clinical Trial Reporting Program )
First Posted: March 22, 2017    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018

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

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Bronchial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Carcinoma
Naloxegol
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents