Patient case: 52-year-old male with Lung cancer. Genetic variant: EML4-ALK Fusion transcript. Other conditions: Hypertension, Osteoarthritis.

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

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.

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.
  TERTIARY OBJECTIVES:
  I. To examine if MOR expression or activation is a prognostic marker in advanced NSCLC, and whether its expression/activation can be used to guide pain management.
  OUTLINE: Patients are randomized to 1 of 3 groups.
  GROUP I (LOWER DOSE NALOXEGOL): Patients receive lower dose naloxegol orally (PO) once daily (QD) and placebo PO QD. Courses repeat every 3 weeks in the absence of unacceptable toxicity.
  GROUP II (HIGHER DOSE NALOXEGOL): Patients receive placebo PO QD and higher dose naloxegol PO QD. Courses repeat every 3 weeks in the absence of unacceptable toxicity.
  GROUP III (PLACEBO): Patients receive placebo PO QD. Courses repeat every 3 weeks in the absence of unacceptable toxicity.
  After completion of study treatment, patients are followed up every 3 months.

Eligibility: Inclusion Criteria:
  -  Advanced (stage IIIB or IV) lung adenocarcinoma diagnosed by biopsy of the primary or metastatic site
  -  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; 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
  -  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)
  -  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)

Relevance to patient case: not relevant