The patient has known and active alcohol or drug dependency
History of or ongoing alcohol abuse that, in the opinion of the investigator, would compromise compliance or impart excess risks associated with study participation
Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
Alcohol dependency within 6 months before study entry
Willing to remain abstinent from consuming alcohol.
Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol, including patients with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol. Patients planning to take a vacation for 14 or more consecutive days during the course of the study are ineligible.
Participant is an active alcoholic or consumes excessive amounts of alcohol per the following definitions:\r\n* Female: More than 3 drinks on any day or a total of more than seven drinks in a week\r\n* Male: More than 4 drinks on any day or a total of more than 14 drinks in a week\r\n** 1 drink = \r\n*** Beer: 12 oz. (1 standard size can or bottle)\r\n*** Wine: 5 oz. (one standard glass)\r\n*** Spirits: 6 oz. (one mixed drink or one 1.5 fluid oz. shot)
Regular and excessive use of alcohol within the 6 months prior to study entry defined as alcohol intake > 14 drinks per week in a man or > 7 drinks per week in a woman. Approximately 10 g of alcohol equals one \drink\ unit. One unit equals 1 ounce of distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine.
Ability to comply with dietary and tobacco/alcohol abstinence requirements.
Active alcohol use disorder or hazardous drinking; this will be screened with the Alcohol Use Disorders Identification Test (AUDIT-C), and positive scores (4 or greater for men and 3 or greater for women) will result in study clinician assessment and discretion
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Center for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men
Patients in active alcohol withdrawal
Willingness to abstain from alcohol or any alcohol-containing fluids for the duration of the study
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men; patients who feel they cannot comply with this recommendation are not eligible
Willing to limit daily alcohol intake to the following: one 12-oz glass of beer, one 6-oz glass of wine, or one 1.5-oz portion of 80-proof alcohol
Willing to remain abstinent from consuming alcohol while on DSF
Subject is a chronic alcoholic (intake > 35 units of alcohol (>5 bottles of wine weekly)) or drug abuser
Subjects with a known hypersensitivity to fulvestrant or any of its formulation components including castor oil, alcohol, benzyl alcohol, and benzyl benzoate.
4 or above for men OR 3 or above for women on the Alcohol Use Disorders Identification Test (AUDIT-C) are considered a “positive” screen and will require additional clinician assessment to determine if an alcohol use disorder is present
Use of alcohol or drug use that may interfere with the patient's ability to participate in the study.
Ongoing alcohol use or abuse defined as > an average of 2 alcoholic beverages daily
Willingness to reduce alcohol consumption during study to 2 or fewer standard drinks/day (3 oz. of alcohol or two beers (12 oz.), or two 5 oz. glasses of wine).
Evidence of problem alcohol consumption based on AUDIT.
DOSE ESCALATION COHORT: Subjects with clinical condition where subjects may not tolerate immune mediated hepatotoxicity; this includes extensive liver metastasis, excessive intake of alcohol (male > 4 drinks/day, female > 2 drinks/day), and the use of acetaminophen > 2 gms/day; per epacadostat investigator’s brochure
DOSE EXPANSION COHORT: Subjects with clinical condition where subjects may not tolerate immune mediated hepatotoxicity; this includes extensive liver metastasis, excessive intake of alcohol (male > 4 drinks/day, female > 2 drinks/day), and the use of acetaminophen > 2 gms/day; per epacadostat investigator’s brochure
Unable to abstain from alcohol for the duration of the study
Excessive alcohol intake should be avoided (occasional use is permitted)
Regular alcohol consumption averaging more than seven drinks/week for women and 14 drinks/week for men within 6 months of screening.
History of any hepatitis (e.g. alcohol or non-alcohol steatohepatitis (NASH), drug- related, autoimmune)
The following agents are not permitted while patients are taking MLN8237, and should be discontinued at prior to registration if patients are taking them:\r\n* Patients must stop using the proton pump inhibitor (PPI) for at least 4 days prior to the first dose of MLN8237; administration of PPI while on study is not permitted\r\n* Histamine-2 (H2) receptor antagonists are not permitted from the day prior through to the end of MLN8237 dosing, except as required for premedication for rituximab; constant dosing of H2 blockers is not permitted\r\n* Antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237\r\n* Administration of pancreatic enzymes is not permitted at any time while on study\r\n* Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine or St. John's wort is not permitted\r\n* Concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; if bisphosphonate therapy is initiated after study entry, bone lesions will not be considered evaluable for disease response\r\n* Patients must be willing not drive, operate dangerous tools or machinery, or engage in any other potentially hazardous activity that requires full alertness and coordination if they experience excessive sedation; if a patient experiences excessive sedation believed to be related to MLN8237, treatment with MLN8237 should be interrupted\r\n* Patients must be willing to limit alcohol consumption to no more than 1 standard unit of alcohol (12 oz beer [350 mL], 1.5 oz [45 mL] of 80-proof alcohol, or one 6-oz [175 mL] glass of wine) per day during the study and for 30 days from the last dose of MLN8237; minimize the use of agents with central nervous system (CNS) effects\r\n* Benzodiazepine use is discouraged but not prohibited
Chronic or planned acute alcohol use of 3 or more drinks per day
History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis [NASH], auto immune, or grade 3-4 drug-related hepatitis)
Daily consumption of alcohol exceeding 3 standard drinks a day (defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor)
Phase 1b subject is unable to avoid alcohol or tobacco consumption for the duration of the study.
Willing to remain abstinent from consuming alcohol while on disulfiram
Excessive alcohol intake (more than 3 alcoholic beverages per day) should be avoided (occasional use is permitted)
History of excessive alcohol consumption
Have a recent history of alcoholism; former alcoholics who have abstained from alcohol for 5 years or more may be enrolled in this study
Have an active chemical or alcohol dependency as assessed by the investigator
Subjects who are known to be actively abusing alcohol or drugs
Patient agrees to consume no more than 1 standard unit of alcohol per day during the study and for 30 days from the last dose of alisertib; a standard unit of alcohol is defined as a 12 oz beer (350 mL), 1.5 oz (45 mL) of 80-proof alcohol, or one 6-oz (175 mL) glass of wine
Subject must be willing to limit alcohol to moderate use which is defined as: up to one drink a day for women or two drinks a day for men; examples of one drink include:\r\n* Beer: 12 fluid ounces (355 milliliters)\r\n* Wine: 5 fluid ounces (148 milliliters)\r\n* Distilled spirits (80 proof): 1.5 fluid ounces (44 milliliters)
Patients with a history of excessive alcohol intake which is defined in accordance with Centers for Disease Control and Prevention (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men
Patients with a history of alcohol abuse, or patients unwilling or unable to remain completely abstinent of alcohol during the study period
PART I: Participants who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30 mL distilled spirits, 340 mL beer, or 120 mL wine) will not be allowed
PART II: Those who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30 mL distilled spirits, 340 mL beer, or 120 mL wine) will not be allowed
Alcohol abuse problems make patients INELIGIBLE; patients need to be consuming less than or equal to 14 units of alcohol weekly
History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-related, auto-immune)
Alcohol consumption within 30 days of first study treatment, or refusing to abstain from alcohol for the duration of study treatment
History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis [NASH], auto immune, or grade 3-4 drug-related hepatitis)
Refusal to modify or reduce excessive alcohol use that is likely to interfere with an individual’s sleep
Other exclusion criteria include: illicit drug use, shift work, current dieting, excessive regular use of alcohol (more than two 5 ounce glasses of wine or equivalents/day) or a history of binge drinking (more than 7 drinks/24 hour period) within the last 6 months
Self-reported consumption of > 14 alcoholic drinks per week or positive screening on the CAGE questionnaire in relation to the past year; NOTE: A single, standard alcoholic drink is defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor
Patients with a current history (in the past 30 days) of heavy drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men. A standard drink contains .6 ounces of pure alcohol. Generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey). While on study, patients should limit their alcohol consumption to no more than 8 drinks
Subjects who have been drinking > 5 alcoholic drinks daily for the last year
Refusal to modify or reduce excessive alcohol use that is likely to interfere with an individual’s sleep
Chronic excessive use of psycho-pharmaceuticals, alcohol, illicit drugs, or narcotics
Patients with suspected or confirmed poor compliance, mental instability, or prior or current alcohol or drug abuse deemed by the investigator to be likely to affect their ability to sign the informed consent, or undergo study procedures will be excluded
Alcohol intake > 3 oz/day
Recent active excessive alcohol or illicit drug use
Current alcohol over-use as defined by currently consuming 4 drinks or more per day or binge drinking (6 or more drinks in one night) within the past week
Patients with a current history (in the past 30 days) of heaving drinking which is defined in accordance with Centers for Disease Control and Prevention (CDC) definition as more than 8 drinks per week for women and more than 15 drinks per week for men; a standard drink contains .6 ounces of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey); while on study, patients should limit their alcohol consumption to no more than 8 drinks per week for women and no more than 15 drinks per week for men; patients who feel they cannot comply with this recommendation are not eligible
Consume excessive amounts of alcohol (> 30 drinks/week)
Caregivers: Alcohol consumption less than 2 drinks/day
Other exclusion criteria include: illicit drug use, shift work, current dieting, excessive regular use of alcohol (more than two 5 ounce glasses of wine or equivalents/day) or a history of binge drinking (more than 7 drinks/24 hour period) within the last 6 months
Chronic alcohol abuse (> 6 alcoholic beverages daily)
Willingness to avoid excessive use of alcohol during the study; note: excessive use is defined as drinking >= 8 alcoholic drinks per week on average
Self-reported consumption of more than 4 alcoholic drinks per day
Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
Current excessive alcohol consumption (average alcohol consumption of more than 5 drinks per day)
Intake of alcohol, food or beverages (e.g., grapefruit, cranberry, pomegranate and aloe vera juices, German chamomile) known to interfere with either CYP3A4 or CYP2D6 metabolic enzymes within 1 week prior to Day 1 and during the overall study period.
Blood alcohol level > 0.01 (one re-screen allowed)
Binge alcohol drinking (4/5 [female/male] drinks per day more than 9 days in the past month)
Are alcohol consumers (defined as an average consumption of greater than 1 drink/day over one week [wk] [one drink = 1 oz. liquor, 12 oz. beer])
Current heavy alcohol consumption (greater than or equal to 6 drinks/day, 6 days/week)
For Zyban:\r\n* Pregnant or breast feeding or planning to become pregnant in the next 6 months\r\n* History of seizure disorder or head trauma\r\n* History of severe allergic reaction to Zyban (also known as Wellbutrin, Bupropion)\r\n* History of eating disorder, such as anorexia or bulimia, which is overeating and throwing up\r\n* Currently taking Wellbutrin, Zyban or any other medications that contain bupropion\r\n* History of alcohol or substance abuse in the past year\r\n* Current excessive alcohol consumption defined as 14 or more alcoholic drinks per week and/or binge drinking (5 or more drinks on one occasion) 2 or more times in the past month\r\n* Use of monoamine oxidase (MAO) inhibitors, such as Nardil, tranylcypromine, phenelzine, or Parnate\r\n* Reported use of illegal drugs (opiates, cocaine, narcotics, or other stimulants such as diet pills)\r\n* Use of psychoactive medications, such as fluoxetine, doxepin, clonidine, or buspirone\r\n* Use of benzodiazepines, such as Xanax, Valium, Ativan, Klonopin in the past 2 weeks
Concurrent excessive alcohol consumption (average alcohol consumption of more than 5 drinks per day)
History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months
Willing to use alcohol in moderation while taking study agent
Patients with history of chronic alcohol use
Chronic alcohol use defined as > 2 standard drinks per day (more than 2 beers, 2 glasses of wine, or 2 shots of liquor per day)
Participants with bleeding diathesis, history of gastric/duodenal ulcers in the last 5 years, NSAID-precipitated bronchospasm, patients unwilling or unable to limit alcohol consumption to i.e. =< 3 alcohol drinks a day
Have a history of alcoholism or high alcohol consumption (average of > 3 standard drinks/day)
Self-reported consumption of more than 4 alcoholic drinks per day
Patients who are on disulfiram, metronidazole or are dependent on alcohol
Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
History of alcohol or drug dependency in the past year
HEALTHY VOLUNTEER: Evidence of current ongoing illicit drug use or average alcohol use of greater than 2 drinks a day
History of ongoing alcohol abuse or binge drinking; alcohol abuse will be defined as a pattern of drinking that results in harm to one’s health, interpersonal relationships, and ability to work; binge drinking will be defined as at least one episode of consuming more than five units in men and four units in women during the previous month; one unit of alcohol can generally said to be a half pint of beer, a single measure (shot glass) of a spirit or a small glass of table wine
Patients with a history of excessive alcohol intake which is defined in accordance with Centers for Disease Control and Prevention (CDC) definitions as more than 1 drink per day for women and more than 2 drinks per day for men; this definition is referring to the amount consumed on any single day and is not intended as an average over several days; a standard drink is equal to 13.7 grams (0.6 ounces) of pure alcohol; generally, this amount of pure alcohol is found in 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a “shot” of 80-proof distilled spirits or liquor (e.g., gin, rum, vodka, or whiskey)
Ability and willingness to completely abstain from alcohol consumption for 3 days prior to kava administration, continuing until a minimum of 7 days after kava administration
Known history of uncontrolled sleep apnea syndrome, or sleep apnea requiring supplemental oxygen, and other conditions that could result in excessive daytime sleepiness
As per self report, participant has another sleep disorder provided that it is not adequately treated (e.g., sleep apnea without continuous positive airway pressure [CPAP] treatment)
No history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease, or requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease or a requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease requiring supplemental oxygen
Hematocrit > 50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure (per Endocrine Society Clinical Practice Guidelines)
Untreated, uncontrolled Sleep apnea
Ejection fraction (EF) < 40% or myocardial infarction (MI) within the past 3 months; known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
Patients who have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness (such as severe chronic obstructive pulmonary disease or requirement for supplemental oxygen) are not eligible
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; patients who use continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP) at night and have controlled sleep apnea syndrome are allowed
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen, or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Patient must not have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease
Known history of uncontrolled sleep apnea syndrome and other conditions according to enrolling investigator that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen therapy; or requirement of recurrent thoracentesis to manage pleural effusions
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
History of uncontrolled sleep apnea syndrome or other condition that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
Have a confirmed diagnosis of sleep apnea or restless leg syndrome
Have diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated (as assessed by screening questions)
Have a diagnosed sleep disorder (i.e., obstructive sleep apnea or narcolepsy)
Motivated and able to follow the demands of the SHUTi program, to keep sleep records, complete self-report symptom reports and make changes in their sleep schedule, including restricting their sleep
Diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated, or other sleep disorder
Motivated and able to follow the demands of the CBTI-CS program, to keep sleep records, complete self-report symptom reports and make changes in their sleep schedule, including restricting their sleep
Have diagnosed, untreated sleep apnea or sleep apnea suspected by a physician but which has not been unevaluated or other sleep disorder
Has a self-reported history of diagnosed sleep disorders (e.g., obstructive sleep apnea, insomnia), comorbidities associated with poor sleep or fatigue (e.g., chronic fatigue syndrome), or a job with night shifts
Sleep apnea or restless leg syndrome (RLS)
Have a diagnosed sleep disorder including untreated obstructive sleep apnea, periodic limb movement disorder, or restless leg syndrome
Sleep apnea
Participant has known sleep apnea or medically treated sleep disorder (e.g. restless leg syndrome)
Patients with a diagnosis of polysomnographically confirmed obstructive sleep apnea or narcolepsy
Use of medication for treatment of another sleep disorder, such as restless leg syndrome or narcolepsy
untreated sleep disorders such as sleep apnea
Have a clinical diagnosis of sleep apnea or restless leg syndrome
Experiencing disrupted sleep (determined by Pittsburgh Sleep Quality Index)
No diagnosis of sleep apnea or restless leg syndrome that is currently interfering with sleep
Has a sleep disorder (including insomnia, delayed sleep phase syndrome [DSPS], narcolepsy, night terror, sleep apnea, sleep walking)