Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
12

Inclusion Criteria

Life expectancy of at least 6 months
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
Hemoglobin > 11g/dL
...
Life expectancy of at least 6 months
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
Hemoglobin > 11g/dL
Ability to understand and the willingness to sign a written informed consent document
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
Prothrombin time (PT), international normalized ratio (INR) less than 1.5 times the institutional upper limit of normal
Total bilirubin < 1.5 x institutional upper limit of normal
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
Pre-surgery tumor deemed amenable to core biopsy (with at least 100 mm^3 tumor volume per biopsy)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky > 70%)
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
Platelets >= 100,000/mcL
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,000/mcL
Any human leukocyte antigen (HLA) type
Women of all races and ethnic groups are eligible for this trial
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)

Exclusion Criteria

Unable or unwilling to swallow tablets BID
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
Mild Raynaud's phenomenon
...
Unable or unwilling to swallow tablets BID
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
Mild Raynaud's phenomenon
Unstable angina pectoris
Congestive heart failure
The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is 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
Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs; any cyclooxygenase-2 (COX-2) inhibitors are permitted
Patients who have had prior systemic therapy or radiotherapy for stage III or IV epithelial ovarian, fallopian or primary peritoneal carcinoma
Malabsorption syndrome or chronic nausea that might hinder absorption and assessment of oral medication
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
Cardiac arrhythmia
Therapy with monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitor (SSRIs) within the last 4 weeks or history of serotonin syndrome
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
History of pulmonary embolus and/or substantial deep vein thrombosis
Pregnancy or nursing or unwilling to take adequate birth control during therapy; NOTE: breastfeeding should be discontinued
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)
The presence of laboratory evidence of autoimmune disease (e.g. positive antinuclear antibody [ANA] titer) without associated symptoms
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
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
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)
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
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)
Psychiatric illness/social situations that would limit compliance with study requirements
Subjects with any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol
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
Inhaled corticosteroids are permitted
Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder
Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease
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

Summary

Conditions
  • Stage III Primary Peritoneal Cancer AJCC v7
  • Stage III Fallopian Tube Cancer AJCC v7
  • Stage III Ovarian Cancer AJCC v6 and v7
  • Stage IIIA Fallopian Tube Cancer AJCC v7
  • Stage IIIA Ovarian Cancer AJCC v6 and v7
  • Stage IIIA Primary Peritoneal Cancer AJCC v7
  • Stage IIIB Fallopian Tube Cancer AJCC v7
  • Stage IIIB Ovarian Cancer AJCC v6 and v7
  • Stage IV Primary Peritoneal Cancer AJCC v7
  • Stage IIIB Primary Peritoneal Cancer AJCC v7
  • Stage IIIC Fallopian Tube Cancer AJCC v7
  • Stage IIIC Ovarian Cancer AJCC v6 and v7
  • Stage IIIC Primary Peritoneal Cancer AJCC v7
  • Stage IV Ovarian Cancer AJCC v6 and v7
  • Stage IV Fallopian Tube Cancer AJCC v6 and v7
Type
Interventional
Phase
Early Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 19 years and 125 years
Gender
Only females

Description

PRIMARY OBJECTIVES: I. To determine the extent by which INCB024360 (epacadostat) alters the number of cluster of differentiation (CD)8+ T cells by immunohistochemistry (IHC). SECONDARY OBJECTIVES: I. To determine the extent by which INCB024360 alters the number and character of tumor infiltrating ly...

PRIMARY OBJECTIVES: I. To determine the extent by which INCB024360 (epacadostat) alters the number of cluster of differentiation (CD)8+ T cells by immunohistochemistry (IHC). SECONDARY OBJECTIVES: I. To determine the extent by which INCB024360 alters the number and character of tumor infiltrating lymphocytes by IHC and gene signature by microarray analysis. II. To determine the extent to which INCB024360 alters the character of the cellular content of peripheral blood mononuclear cells (PBMCs) and ascites fluid as determined by multiparameter flow cytometry. III. To determine the extent to which INCB024360 alters PBMC and ascites fluid transcriptomes. IV. To determine whether INCB024360 alters the ongoing and nascent anti-tumor responses antigens associated with ovarian cancer (e.g., cancer/testis antigen 1B [NY-ESO-1], preferentially expressed antigen in melanoma [PRAME] and mesothelin) as well as memory viral responses (influenza A), and chronic viral responses (cytomegalovirus). V. To assess the safety and tolerability of INCB024360. VI. To determine the extent to which a regimen of INCB024360 that normalizes serum kynurenine/tryptophan (Kyn/Trp) ratios will alter the tumor microenvironment by assessing the ascites and intra-tumor Kyn/Trp ratios at the time of surgery, one day after stopping INCB024360. VII. To associate any observed changes with the expression of IDO1 protein by IHC in tumor or tumor infiltrating cells. OUTLINE: Patients receive epacadostat orally (PO) twice daily (BID) on days 1-14 and undergo surgery on day 15. Treatment continues in the absence of disease progression or unacceptable toxicity. In circumstances where there are medical or administrative reasons for delaying surgery, treatment with epacadostat may continue for up to 3 weeks. After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria

Life expectancy of at least 6 months
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
Hemoglobin > 11g/dL
...
Life expectancy of at least 6 months
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
Hemoglobin > 11g/dL
Ability to understand and the willingness to sign a written informed consent document
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
Prothrombin time (PT), international normalized ratio (INR) less than 1.5 times the institutional upper limit of normal
Total bilirubin < 1.5 x institutional upper limit of normal
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
Pre-surgery tumor deemed amenable to core biopsy (with at least 100 mm^3 tumor volume per biopsy)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky > 70%)
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
Platelets >= 100,000/mcL
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,000/mcL
Any human leukocyte antigen (HLA) type
Women of all races and ethnic groups are eligible for this trial
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)

Exclusion Criteria

Unable or unwilling to swallow tablets BID
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
Mild Raynaud's phenomenon
...
Unable or unwilling to swallow tablets BID
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
Mild Raynaud's phenomenon
Unstable angina pectoris
Congestive heart failure
The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is 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
Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs; any cyclooxygenase-2 (COX-2) inhibitors are permitted
Patients who have had prior systemic therapy or radiotherapy for stage III or IV epithelial ovarian, fallopian or primary peritoneal carcinoma
Malabsorption syndrome or chronic nausea that might hinder absorption and assessment of oral medication
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or medical (e.g. infectious) illness
Cardiac arrhythmia
Therapy with monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitor (SSRIs) within the last 4 weeks or history of serotonin syndrome
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
History of pulmonary embolus and/or substantial deep vein thrombosis
Pregnancy or nursing or unwilling to take adequate birth control during therapy; NOTE: breastfeeding should be discontinued
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)
The presence of laboratory evidence of autoimmune disease (e.g. positive antinuclear antibody [ANA] titer) without associated symptoms
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
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
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)
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
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)
Psychiatric illness/social situations that would limit compliance with study requirements
Subjects with any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the subject or compliance with the protocol
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
Inhaled corticosteroids are permitted
Known human immunodeficiency virus (HIV) or other history of immunodeficiency disorder
Extensive active brain disease including symptomatic brain metastases or presence of leptomeningeal disease
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

Locations

Buffalo, New York, 14263
Minneapolis, Minnesota, 55455
Buffalo, New York, 14263
Minneapolis, Minnesota, 55455

Tracking Information

NCT #
NCT02042430
Collaborators
Not Provided
Investigators
  • Principal Investigator: Kunle Odunsi Cancer Immunotherapy Trials Network
  • Kunle Odunsi Cancer Immunotherapy Trials Network