INCB024360 Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02042430
First received: January 20, 2014
Last updated: October 13, 2014
Last verified: June 2014
  Purpose

This pilot clinical trial studies indoleamine 2,3-dioxygenase (IDO1) inhibitor INCB024360 (INCB024360) before surgery in treating patients with newly diagnosed stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. IDO1 inhibitor INCB024360 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIA Primary Peritoneal Cavity Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIB Primary Peritoneal Cavity Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IIIC Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: IDO1 inhibitor INCB024360
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of the Immunological Effects of Neo-Adjuvant INCB024360 in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of participants with an increase in CD8+ T cells [ Time Frame: Baseline to day 15 ] [ Designated as safety issue: No ]
    The correlation between results of the IDO expression levels analyzed by IHC and the Kyn/Trp ratios will be analyzed if available.


Secondary Outcome Measures:
  • Change in number and character of tumor infiltrating lymphocytes [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in gene signatures as assessed by microarray analysis [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in character of the cellular content of PBMCs and ascites fluid, determined by multiparameter flow cytometry [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in fluid transcriptomes in PBMC and ascites [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in ongoing and nascent anti-tumor response antigens associated with ovarian cancer, including NY-ESO-1, PRAME and mesothelin [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in memory viral responses, including influenza A [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Change in chronic viral responses, including cytomegalovirus [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]
  • Incidence of adverse events, assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
  • Kyn/Trp ratios [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Changes in IDO1 expression by IHC [ Time Frame: Baseline to up to day 35 ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: December 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (IDO1 inhibitor INCB024360)
Patients receive IDO1 inhibitor INCB024360 PO 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 IDO1 inhibitor INCB024360 may continue for up to 3 weeks.
Drug: IDO1 inhibitor INCB024360
Given PO
Other Names:
  • INCB024360
  • indoleamine-2,3-dioxygenase inhibitor INCB024360
Procedure: therapeutic conventional surgery
Undergo surgery
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the extent by which INCB024360 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 IDO1 inhibitor INCB024360 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 IDO1 inhibitor INCB024360 may continue for up to 3 weeks.

After completion of study treatment, patients are followed up for 1 year.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  • 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) within institutional limits
  • International normalized ratio (INR) within institutional limits
  • 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
  • Subjects who are currently receiving therapy with a potent cytochrome P450, subfamily IIIA, polypeptide 4 (CYP3A4) inducer or inhibitor; subjects may enter screening when therapy with the potent inhibitor or inducer is completed
  • Use of any UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid from screening through follow-up period
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02042430

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Melissa A. Geller    612-626-2613    gelle005@umn.edu   
Principal Investigator: Melissa A. Geller         
University of Minnesota Medical Center-Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Melissa A. Geller    612-624-2620      
Principal Investigator: Melissa A. Geller         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Kunle Odunsi    877-275-7724      
Principal Investigator: Kunle Odunsi         
Sponsors and Collaborators
Investigators
Principal Investigator: Kunle Odunsi Cancer Immunotherapy Trials Network
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02042430     History of Changes
Other Study ID Numbers: NCI-2013-02483, NCI-2013-02483, ICD 10033159, ICD 10016180, ICD 10026669, CITN-05 Ovarian IDO, CITN-05, U01CA154967
Study First Received: January 20, 2014
Last Updated: October 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 22, 2014