Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma
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|ClinicalTrials.gov Identifier: NCT01961115|
Recruitment Status : Completed
First Posted : October 11, 2013
Results First Posted : February 7, 2018
Last Update Posted : June 8, 2018
|Condition or disease||Intervention/treatment||Phase|
|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 Biological: MELITAC 12.1 Peptide Vaccine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||September 13, 2013|
|Actual Primary Completion Date :||October 31, 2016|
|Actual Study Completion Date :||May 18, 2017|
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.
Biological: MELITAC 12.1 Peptide Vaccine
- Changes in the Concentration and Number of CD8+ Cells Infiltrating Tumor by IHC by Normalization of Kyn/Trp Ratios. [ Time Frame: Baseline to up to day 21 ]Immunohistochemistry: Tumors were assessed by IHC for pattern of T-cell distribution and infiltration of cells expressing CD3 and CD8.
- Changes in the Concentration and Number of CD8+ Cells Infiltrating Tumor by IHC by Normalization of Kyn/Trp Ratios in Combination With MELITAC 12.1 [ Time Frame: Day 21 up to Day 42 ]Immunohistochemistry: Tumors (day 21 & day 42) were assessed by IHC for pattern of T-cell distribution and infiltration of cells expressing CD3 and CD8.
- Change in PBMC Transcriptome_v2 [ Time Frame: Baseline to up to 16 week ]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_v2 [ Time Frame: Baseline to up to 1 year ]
- Changes in Expression of IDO1 Protein by IHC in Tumor or Tumor-infiltrating Cells_v2 [ Time Frame: Baseline to 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_v2 [ 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_v2 [ Time Frame: Up to 1 year ]
- Overall Response Rate Using the RECIST or Immune-Related Response Criteria (irRC)_v2 [ Time Frame: Up to 1 year ]
- Overall Survival_v2 [ 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_v2 [ Time Frame: Up to 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|