Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

Recurrent Melanoma Clinical Trial

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

Status Completed

Clinical Trial Summary

This pilot phase II trial studies how well epacadostat and vaccine therapy work in treating patients with stage III-IV melanoma. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vaccines made from peptides and antigens may help the body build an effective immune response to kill tumor cells. Giving epacadostat with vaccine therapy may be an effective treatment for advanced melanoma.

Clinical Trial Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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. ;

Related Conditions & MeSH terms

• 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
• Uveal Neoplasms

• NCT number: NCT01961115
• Study type: Interventional
• Source: Fred Hutchinson Cancer Research Center
• Status: Completed
• Phase: Phase 2
• Start date: September 13, 2013
• Completion date: May 18, 2017