| Eligibility |
Inclusion Criteria:
- Newly diagnosed stage III or IV epithelial ovarian, fallopian or primary peritoneal
carcinoma with or without ascites and potentially resectable disease agreeing to
debulking surgery as standard therapy
- Pre-surgery tumor deemed amenable to core biopsy (with at least 100 mm^3 tumor volume
per biopsy)
- Patients must be willing and able to undergo ascites fluid collection pre- and
post-study treatment if adequate ascites is present; patients without adequate ascites
may also participate in the trial
- Patients must be willing and able to undergo a pre-surgery biopsy and wait 2 weeks
before their debulking surgery; NOTE: consented patients with subsequent inadequate
biopsy material will not receive INCB024360 or be analyzed and will be replaced; the
study will be stopped if adequate tissue is not obtained in more than 2/3 of paired
samples with a maximum accrual of 18 patients
- Women of all races and ethnic groups are eligible for this trial
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky > 70%)
- Any human leukocyte antigen (HLA) type
- Life expectancy of at least 6 months
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Hemoglobin > 11g/dL
- Total bilirubin < 1.5 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
up to 2.5 times upper limit of normal (ULN)
- Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance > 60
ml/min OR > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional
normal
- Prothrombin time (PT), international normalized ratio (INR) less than 1.5 times the
institutional upper limit of normal
- Females of childbearing potential must have a negative pregnancy test within 48 hours
prior to initiation of protocol therapy; women of child-bearing potential must agree
to use adequate contraception prior to study entry and for the duration of study
participation, and 4 months after completion of INCB024360; effective birth control
includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2 barrier
methods; effective barrier methods are male or female condoms, diaphragms, and
spermicides (creams or gels that contain a chemical to kill sperm) (c) oral
contraceptive pills and (d) intramuscular DEPO medroxyprogesterone acetate; should a
woman become pregnant or suspect she is pregnant while she is participating in this
study, she should inform her treating physician immediately
- NOTE: subjects are considered not of childbearing potential if they are
surgically sterile, they have undergone a hysterectomy, bilateral tubal ligation,
or bilateral oophorectomy or they are postmenopausal; menopause is the age
associated with complete cessation of menstrual cycles, menses, and implies the
loss of reproductive potential; by a practical definition, it assumes menopause
after 1 year without menses with an appropriate clinical profile at the
appropriate age
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had prior systemic therapy or radiotherapy for stage III or IV
epithelial ovarian, fallopian or primary peritoneal carcinoma
- Extensive active brain disease including symptomatic brain metastases or presence of
leptomeningeal disease
- Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal
anti-inflammatory drugs; any cyclooxygenase-2 (COX-2) inhibitors are permitted
- Use of any UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor
including: acitretin, amitriptyline, androsterone, cyclosporine, dasatinib,
diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide,
gefitinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine,
ketoconazole, linoleic acid, mefenamic acid, mycophenolic acid, niflumic acid,
nilotinib, phenobarbital, phenylbutazone, phenytoin, and probenecid propofol,
quinidine, ritonavir, sorafenib, sulfinpyrazone, valproic acid, and verapamil;
patients must avoid UGT1A9 inhibitors from the screening period through active
treatment with INCB024360 and for one week after discontinuation of INCB024360
- Uncontrolled intercurrent illness including, but not limited to:
- Unstable angina pectoris
- Cardiac arrhythmia
- Congestive heart failure
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Medical or psychiatric illness that would, in the opinion of the investigator,
preclude participation in the study or the ability of patients to provide
informed consent for themselves
- Pregnancy or nursing or unwilling to take adequate birth control during therapy; NOTE:
breastfeeding should be discontinued
- Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder
- Patients who had, within the past 6 months, a cardiovascular accident (CVA) or at risk
for arterial thrombus such as severe peripheral vascular disease (PVD) and carotid
artery disease (CAD)
- History of autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or
autoimmune disorders with visceral involvement; active or inactive auto-immune
disorders (e.g., rheumatoid arthritis, moderate or severe psoriasis, multiple
sclerosis, systemic lupus erythematosus, inflammatory bowel disease, etc.) requiring
treatment
- The following will not be exclusionary:
- Vitiligo, thyroiditis or eczema requiring systemic steroids at a dose =< 7.5
mg/day of prednisone or equivalent; individual cases can be discussed with
the principal investigator
- History of pulmonary disease such as emphysema or chronic obstructive pulmonary
disease (COPD), (forced expiratory volume of the lung in 1 second [FEV1] > 60% of
predicted for height and age); pulmonary function tests (PFTs) are required in
patients with prolonged smoking history or signs, symptoms, or history of respiratory
dysfunction)
- Cirrhosis or chronic hepatitis C virus positivity or chronic hepatitis B infection;
subjects who may not tolerate immune-mediated hepatitis due to compromised hepatic
reserve are also excluded from participation including: 1) subjects with extensive
liver metastasis (as judged by the investigator) 2) subjects who drink more than two
standard alcoholic beverages per day on a regular basis 3) subjects who consume more
than 2 grams of acetaminophen per day on a regular basis
- A positive hepatitis B serology indicative of previous immunization (i.e.,
hepatitis B surface antibody [HBsAb] positive and hepatitis B core antibody
[HBcAb] negative), or a fully resolved acute hepatitis B virus (HBV) infection is
not an exclusion criterion
- Concurrent systemic immunosuppressive therapy or steroid therapy with more than 7
consecutive days of steroids within the last 4 weeks
- The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10
mg/day) as replacement therapy is permitted
- Inhaled corticosteroids are permitted
- The following will not be exclusionary:
- The presence of laboratory evidence of autoimmune disease (e.g. positive
antinuclear antibody [ANA] titer) without associated symptoms
- Mild Raynaud's phenomenon
- History of severe asthma, as defined by prior or current use of systemic
corticosteroids for disease control, with the exception of physiological
replacement doses of cortisone acetate or equivalent, as defined by a dose
of prednisone or equivalent of 10 mg or less
- Malabsorption syndrome or chronic nausea that might hinder absorption and assessment
of oral medication
- Cardiovascular disease that meets one of the following: congestive heart failure (New
York Heart Association class III or IV), active angina pectoris, or recent myocardial
infarction (within the last 6 months)
- History of pulmonary embolus and/or substantial deep vein thrombosis
- Patient with prior malignancies other than ovarian cancer for which the patient has
not been disease free for 3 years or more, except treated and cured basal or squamous
cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
- Therapy with monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake
inhibitor (SSRIs) within the last 4 weeks or history of serotonin syndrome
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or medical (e.g. infectious) illness
- Any underlying medical or psychiatric condition, which in the opinion of the
investigator, will make the administration of INCB024360 hazardous or obscure the
interpretation of adverse events
- Unable or unwilling to swallow tablets BID
- Subjects with any concurrent condition that, in the investigator's opinion, would
jeopardize the safety of the subject or compliance with the protocol
- Low-dose Coumadin (1 mg) is acceptable; however, doses that increase INR are not
permitted; if an alternative to Coumadin-based anticoagulants cannot be used, the INR
should be monitored weekly after initiation of therapy and upon discontinuation of
INCB024360, until INR normalization
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