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

NCT01961115 | Completed Phase 2 Results

• 3 other identifiers: CITN-04NCI-2013-01605U01CA154967
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Changes in the Concentration and Number of CD8+ Cells Infiltrating Tumor by IHC by Normalization of Kyn/Trp Ratios.

  Immunohistochemistry: Tumors were assessed by IHC for pattern of T-cell distribution and infiltration of cells expressing CD3 and CD8.

  Baseline to up to day 21

• 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

  Immunohistochemistry: Tumors (day 21 \& day 42) were assessed by IHC for pattern of T-cell distribution and infiltration of cells expressing CD3 and CD8.

  Day 21 up to Day 42

Secondary Outcomes (8)

• Change in PBMC Transcriptome_v2

  Baseline to up to 16 week

• Change in the Number and Character of PBMC Populations, Including T and NK Cells, as Evaluated by Multiparameter Flow Cytometry_v2

  Baseline to up to 1 year

• Changes in Expression of IDO1 Protein by IHC in Tumor or Tumor-infiltrating Cells_v2

  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

  Baseline to up to 16 weeks

• Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0_v2

  Up to 1 year

Study Arms (1)

Treatment (epacadostat, MELITAC 12.1)

EXPERIMENTAL

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.

Drug: Epacadostat; Biological: MELITAC 12.1 Peptide Vaccine

Interventions

Epacadostat DRUG

Given PO

Also known as: INCB 024360, INCB024360

Treatment (epacadostat, MELITAC 12.1)

MELITAC 12.1 Peptide Vaccine BIOLOGICAL

Given ID/SC

Treatment (epacadostat, MELITAC 12.1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have malignant melanoma validated by histology or cytology; patients may have had primary cutaneous, mucosal, or ocular melanoma or metastasis from an unknown primary site
• NOTE: patients must have measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional chest x-ray or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
• Unresectable stage III or IV validated by clinical criteria (including recurrent melanoma), or patients with multiple skin/soft tissue metastases of melanoma that may be resectable but are judged to have a future recurrence risk exceeding 70% (e.g., large adenopathy, distant skin metastases or multiple in-transit melanoma metastases); tumor deemed amenable to biopsy (excisional, incisional, or core, with at least 100 mm\^3 tumor volume per biopsy date) and fine-needle aspiration (FNA) biopsy
• NOTE: optimally, patients will have tumor approachable for three serial biopsies during the trial; for patients with only one or two tumors approachable for biopsy, available tumor blocks from prior biopsies can serve as the pretreatment sample, but only if formalin-fixed tumor tissue is available and adequate to provide at least 20 unstained slides with sufficient tumor for analysis
• NOTE: patients with unresectable advanced stage III or IV melanoma (including recurrent melanoma) are only eligible if they have failed at least one other first-line systemic therapy (other than adjuvant therapy); exceptions to this requirement are those patients who have refused and/or are ineligible for other systemic therapies
• NOTE: v-raf murine sarcoma viral oncogene homolog B inhibitor (BRAFi) should be considered for all 'unresectable" or metastatic melanoma with BRAFV600E mutation; for low burden in-transit disease patients may enter trial without prior systemic therapy
• Stage IV no evidence of disease (NED) is excluded by this criterion
• Patients may have had prior systemic therapy without constraint on the number of prior treatment regimens except:
• Patients may not have had \> 450 mg/m\^2 doxorubicin
• Patients may not have had \> 3000 centigray (cGy) to fields encompassing the entire pelvis
• Patients must not be on any other systemic therapy within the following intervals before study enrollment:
• week after stereotactic radiosurgery of the brain or comparable technology
• weeks after cytotoxic chemotherapy or external beam radiation therapy
• weeks after chemotherapy regimens including BCNU (carmustine) or mitomycin C
• Patients who experience melanoma progression (by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) while on or after treatment with programmed cell death 1 (PD-1) or PD ligand-1 (PDL-1) antibody may enroll on this study

You may not qualify if:

• Patients who have had cytotoxic chemotherapy, radiotherapy, interferon (IFN), immunosuppressive therapy, or steroids within 4 weeks (6 weeks for nitrosoureas or mitomycin C) before entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier
• Ipilimumab or other immunologically active therapy within 8 weeks of enrollment; NOTE: patients who experience melanoma progression (by RECIST 1.1 criteria) while on or after treatment with PD-1 or PDL-1 antibody may enroll on this study
• Active immunosuppressive therapy, including concurrent systemic immunosuppressive therapy or steroid therapy with more than 7 consecutive days of steroids within the prior 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
• 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 or acute coronary syndrome (within the last 6 months)
• History of peripheral vascular disease (PVD) that has required surgical or percutaneous intervention or documented PVD that requires medical management with medications such as acetylsalicylic acid (ASA) + clopidogrel; patients with diabetes that is not well controlled are excluded from participation; not well controlled is defined as a hemoglobin (Hgb) A1C of greater than 7.5%
• Current or history of systemic autoimmune disease requiring systemic therapy, including significant autoimmunity associated with prior ipilimumab therapy or therapy with antibodies to PD-1 or PD-L1
• Cirrhosis, chronic hepatitis C virus positivity, or chronic hepatitis B infection; subjects who may not tolerate immune-mediated hepatitis due to compromised hepatic reserve also excluded from participation including: subjects with extensive liver metastasis (as judged by the investigator); subjects who drink more than two standard alcoholic beverages per day on a regular basis; subjects who consume more than 2 grams of acetaminophen per day on a regular basis
• Patients who are receiving any other investigational agents for melanoma
• Patients who have had a grade one or grade two gastrointestinal adverse event during or after receiving anti-CTLA-4, anti-PD1 or anti-PD, without a colonoscopy verifying complete resolution of the adverse event
• Patients who have experienced bowel perforation, neurologic involvement, Guillain Barré syndrome, Myasthenia Gravis, Steven Johnson syndrome and other intractable events or grade 4 non-laboratory toxicity
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnancy, nursing, or unwilling to take adequate birth control during therapy
• NOTE: pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with INCB024360 and MELITAC 12.1

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Incyte Corporation: collaborator
• National Cancer Institute (NCI): collaborator
• University of Virginia: collaborator

Study Sites (4)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

epacadostat

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Dr. Martin A. Cheever
• Organization: Fred Hutchinson Cancer Research Center

mcheever@fredhutch.org

206-667-4141

Study Officials

• Craig Slingluff

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 11, 2013
• Study Start: September 13, 2013
• Primary Completion: October 31, 2016
• Study Completion: May 18, 2017
• Last Updated: June 8, 2018
• Results First Posted: February 7, 2018

Record last verified: 2018-05

Locations

US (4)