Naloxegol in Treating Cancer Patients with Opioid-Induced Constipation

Inclusion Criteria

• Patient has the ability to understand and the willingness to sign a written informed consent
• Histologically confirmed cancer diagnosis
• Documented, confirmed OIC defined as less than 3 laxations per week over a 1-week OIC confirmation period at any time during screening and prior to initial treatment period day 1
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3
• Glomerular filtration rate (GFR) greater than or equal to 30 ml/min/1.73 m^2 by modification of diet in renal disease (MDRD)
• Corrected serum calcium less than or equal to 10.5 mg/dL
• Females of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 28 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * A female of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy; or ** 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)
• Females of childbearing potential have a negative pregnancy test within 72 hours prior to initiating study drug dosing
• Patient has an estimated life expectancy greater than or equal to 6 months in the opinion of the investigator
• Patient is able to swallow and retain oral medication

Exclusion Criteria

• Patient has received any of the following agents within 3 days prior to study day 1 and/or are planned to receive throughout the duration of the study: opioid antagonist and mixed agonist/antagonist (e.g. pentazocine, buprenorphine, nalbuphine, naloxone/naloxone combinations, naltrexone/naltrexone combinations, methylnaltrexone, alvimopan), a strong cytochrome P450 family 3 subfamily A polypeptide 4 (CYP3A4) and/or P-glycoprotein 1 (P-gp) inhibitor, a moderate CYP3A4 and/or P-gp inhibitor, and/or a strong CYP3A4 inducer
• Patient is currently receiving or planned to receive concurrent total parenteral nutrition and/or metoclopramide
• Patient is at high risk for bowel perforation
• Patient has constipation that was not primarily caused by opioids, as determined by the investigator
• Patient has a condition that may have affected the permeability of the blood-brain barrier (e.g., known brain metastases, meningeal metastases, brain injury, multiple sclerosis, recent brain injury, uncontrolled epilepsy)
• Patient has clinically active diverticular disease
• Patient has a history of irritable bowel syndrome, signs of active gastrointestinal (GI) bleeding, acute surgical abdomen, bowel stents, indwelling peritoneal catheter, mechanical GI obstruction, fecal impaction, or fecal ostomy
• Patient has motility/neurologic disorders including autonomic failure (spinal cord lesions, tumor invasion of nerves) and/or poorly controlled endocrine/metabolic disorders (hypercalcemia, hypokalemia, diabetes, hypothyroidism), as determined by the investigator
• Patient has uncontrolled cancer pain despite analgesic therapy
• Patient has a severe or uncontrolled medical disorder that would, in the investigator’s opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements)
• Patient has any other condition that, in the opinion of the investigator, may impact the absorption of oral medications
• Patient is pregnant or nursing