Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma
|Mucosal Melanoma Recurrent Melanoma Recurrent Uveal Melanoma Stage IIIA Skin Melanoma Stage IIIA Uveal Melanoma Stage IIIB Skin Melanoma Stage IIIB Uveal Melanoma Stage IIIC Skin Melanoma Stage IIIC Uveal Melanoma Stage IV Skin Melanoma Stage IV Uveal Melanoma||Drug: Epacadostat Other: Laboratory Biomarker Analysis Biological: MELITAC 12.1 Peptide Vaccine||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Pilot Trial of an Indoleamine 2,3, Dioxygenase-1 (IDO1) Inhibitor (INCB024360) Plus a Multipeptide Melanoma Vaccine (MELITAC 12.1) in Patients With Advanced Melanoma|
- Changes in the concentration and number of CD8+ cells infiltrating tumor by IHC [ Time Frame: Baseline to up to 16 weeks ]
- Change in PBMC transcriptome [ Time Frame: Baseline to up to 16 weeks ]Analysis of PBMC gene signature. This may be compared to immunologic response, tumor biopsy data and clinical response.
- Change in the number and character of PBMC populations, including T and NK cells, as evaluated by multiparameter flow cytometry [ Time Frame: Baseline to up to 1 year ]
- Changes in expression of IDO1 protein by IHC in tumor or tumor-infiltrating cells [ Time Frame: Baseline up to 16 weeks ]
- Changes in the level or character of the vaccine-induced CD8+ and CD4+ specific T-cell immune responses by IFN-gamma ELISPOT [ Time Frame: Baseline to up to 16 weeks ]Assessment of immunologic response will be based on a fold-increase measure from baseline as well as using a positivity threshold.
- Incidence of adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]
- Overall response rate using the RECIST or Immune-Related Response Criteria (irRC) [ Time Frame: Up to 1 year ]
- Overall survival [ Time Frame: From the time measurement criteria are met for complete response or partial response until the first date that recurrent and progressive disease is objectively documented, assessed up to 1 year ]
- Time to tumor progression using RECIST or irRC [ Time Frame: Up to 1 year ]
|Actual Study Start Date:||September 13, 2013|
|Primary Completion Date:||September 15, 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (epacadostat, MELITAC 12.1)
Patients receive epacadostat PO BID on days 1-98 and receive MELITAC 12.1 peptide vaccine ID/SC on days 21, 28, 35, 56, 77, and 98 for up to 3 additional courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: MELITAC 12.1 Peptide Vaccine
I. To determine the extent to which a regimen of INCB024360 (epacadostat) that normalizes serum kynurenine (Kyn)/ tryptophan (Trp) ratios alters the tumor microenvironment of melanoma, including determining the number and character of tumor-infiltrating lymphocytes as determined by examination of serial biopsies with immunohistochemistry (IHC) and gene signatures.
II. To determine the extent to which continued INCB024360 treatment plus the addition of the multipeptide melanoma vaccine, MELITAC 12.1 (MELITAC 12.1 peptide vaccine), further alters the tumor microenvironment of melanoma, including determining the number and character of tumor-infiltrating lymphocytes as determined by serial biopsies evaluating IHC and gene signatures.
I. To determine whether a regimen of INCB024360 that normalizes serum Kyn/Trp ratios plus MELITAC 12.1 vaccine changes the level or character of the vaccine-induced clusters of differentiation (CD) 8+ and CD4+ T-cell immune responses as measured in peripheral blood, as compared to prior published experience.
II. To evaluate the extent to which INCB024360 plus MELITAC 12.1 vaccine alters the number and character of peripheral blood mononuclear cell (PBMC) populations, including T and natural killer (NK) cells, as evaluated by multiparameter flow cytometry.
III. To evaluate the extent to which INCB024360 plus MELITAC 12.1 vaccine alters the PBMC transcriptome.
IV. To assess the safety and tolerability of INCB024360 plus MELITAC 12.1 vaccine.
V. To obtain preliminary data on the tumor response rate of INCB024360 plus MELITAC 12.1 vaccine by objective response rate (ORR), time to tumor progression, and overall survival.
VI. 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 1-98 and receive MELITAC 12.1 peptide vaccine intradermally (ID)/subcutaneously (SC) on days 21, 28, 35, 56, 77, and 98. Treatment with epacadostat may repeat every 98 days for up to 3 additional courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01961115
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|United States, Virginia|
|University of Virginia Cancer Center|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||Craig Slingluff||Cancer Immunotherapy Trials Network|