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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion Criteria:

- Advanced (stage IIIB or IV) non-small cell lung cancer 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

- Started first-line systemic therapy of the investigator's choice within 12 weeks prior
to registration, or planning to initiate first-line systemic therapy of the
investigator's choice within 4 weeks 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 (other than current treatment); prior palliative radiation permitted;
prior adjuvant systemic therapy /radiation is permitted

- No more than 7 days of prior use of mixed opioid agonist/opioid antagonists or other
opioid antagonists within 4 weeks before registration; patients should not receive
such medications after registration and for the entire duration of study treatment

- 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, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown; therefore, 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)

- 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)

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Supportive Care
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Terminated
Sponsor
Alliance for Clinical Trials in Oncology

Study Contact

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 systemic therapy. 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 systemic therapy due to adverse events (AEs) and deaths attributable to systemic therapy. After completion of study treatment, patients are followed up every 3 months.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.