Epacadostat Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
|Stage III Fallopian Tube Cancer Stage III Ovarian Cancer Stage III Primary Peritoneal Cancer Stage IIIA Fallopian Tube Cancer Stage IIIA Ovarian Cancer Stage IIIA Primary Peritoneal Cancer Stage IIIB Fallopian Tube Cancer Stage IIIB Ovarian Cancer Stage IIIB Primary Peritoneal Cancer Stage IIIC Fallopian Tube Cancer Stage IIIC Ovarian Cancer Stage IIIC Primary Peritoneal Cancer Stage IV Fallopian Tube Cancer Stage IV Ovarian Cancer Stage IV Primary Peritoneal Cancer||Drug: Epacadostat Other: Laboratory Biomarker Analysis Procedure: Therapeutic Conventional Surgery|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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|
- Number of participants with an increase in CD8+ T cells [ Time Frame: Baseline to day 15 ]The correlation between results of the IDO expression levels analyzed by IHC and the Kyn/Trp ratios will be analyzed if available.
- 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 ]
- Change in chronic viral responses, including cytomegalovirus [ Time Frame: Baseline to up to day 35 ]
- Change in fluid transcriptomes in PBMC and ascites [ Time Frame: Baseline to up to day 35 ]
- Change in gene signatures as assessed by microarray analysis [ Time Frame: Baseline to up to day 35 ]
- Change in memory viral responses, including influenza A [ Time Frame: Baseline to up to day 35 ]
- Change in number and character of tumor infiltrating lymphocytes [ Time Frame: Baseline to up to day 35 ]
- 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 ]
- Changes in IDO1 expression by IHC [ Time Frame: Baseline to up to day 35 ]
- 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 ]
- Kyn/Trp ratios [ Time Frame: Day 15 ]
|Actual Study Start Date:||December 31, 2013|
|Primary Completion Date:||March 31, 2016 (Final data collection date for primary outcome measure)|
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.
Given POOther: Laboratory Biomarker Analysis
Correlative studiesProcedure: Therapeutic Conventional Surgery
I. To determine the extent by which INCB024360 (epacadostat) alters the number of cluster of differentiation (CD)8+ T cells by immunohistochemistry (IHC).
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02042430
|United States, Minnesota|
|University of Minnesota/Masonic Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Kunle Odunsi||Cancer Immunotherapy Trials Network|