Clinical Trial: A Biomarker Study in Advanced Mucosal or Acral Lentiginous Melanoma Receiving Nivolumab in Combination With Ipilimumab

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Study to Estimate the Anti-Tumor Activity and Identify Potential Predictors of Response in Patients With Advanced Mucosal or Acral Lentiginous Melanoma Receiving Standar

Brief Summary: Participants with advanced or metastatic mucosal melanoma (cohort A) and acral lentiginous melanoma (cohort B) eligible for treatment with nivolumab in combination with ipilimumab followed by nivolumab therapy will submit tissue blocks from tumors of malignant melanoma for histopathology review and immunohistochemistry analysis at Georgetown University-Lombardi Comprehensive Cancer Center. Pretreatment blood will be drawn and stored in the Melanoma Research Foundation Breakthrough Consortium Virtual Repository at each participating institution. At the end of participation, samples will be sent to Georgetown University-Lombardi Comprehensive Cancer Center for processing and storage. An optional pretreatment biopsy of an accessible tumor lesion will be performed in a subset of enrolled patients. Patients will receive nivolumab in combination with ipilimumab according to the standard FDA approved treatment regimen.

Detailed Summary:

Immunotherapy with HD-IL-2 has produced durable benefit in 10% of patients with metastatic cutaneous melanoma. The antitumor activity of IL-2 has been limited at least in part by immunosuppressive and immune-regulatory forces within the tumor microenvironment. Antibodies against CTLA4 (e.g. ipilimumab), PD1 and its ligand (PD-L1) produced long-term benefit in approximately 20-40% of patients with advanced melanoma. In addition, the combination of ipilimumab with the anti-PD1 antibody, nivolumab, has shown tumor responses in up to 60% of patients with advanced melanoma. These findings have led to FDA approval of ipilimumab and nivolumab as an indication for treatment of patients with advanced melanoma and nivolumab for other cancers. While these data are exciting, only a few patients enrolled to the prior studies had metastatic MCM or ALM. There is no prospective immunotherapy studies conducted in MCM or ALM-specific population. Therefore the activity of the ipilimumab + nivolumab combination in these subsets or patients remains unknown

Reliable predictive biomarkers for the use of immune checkpoint inhibitors are needed to identify pretreatment those patients most likely to respond and early on in treatment assays could help identify mechanisms of tumor response and resistance necessary to improve therapy. Although tumor PD-L1 expression in tumor confers higher treatment response rate, responses to nivolumab or nivolumab + ipilimumab alone were noted in 55% and 41% of patients, respectively, with PD-L1- tumors. Therefore, more reliable predictive biomarkers are needed.

Recently, extensive studies on metastatic colorectal cancer have demonstrated that a new scoring system as well as density of immune cells infiltrates at the center of the tumor and its invasive margin, described as Immunoscore, could accurately separate a g
Sponsor: Georgetown University

Current Primary Outcome: Objective response rate (ORR) with mucosal melanoma (MCM) [ Time Frame: 24 months ]

ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria and to compare this response rate to the response rate of patients with "good" molecular predictive features


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Objective response rate with acral lentiginous melanoma (ALM) [ Time Frame: 24 months ]
    ORR, defined as complete response [CR] + partial response [PR] per RECIST 1.1 criteria and to compare this response rate to the response rate of patients with "good" molecular predictive features
  • Progression-free survival (PFS) [ Time Frame: 36 months ]
    PFS will be assessed for each cohort
  • Overall survival (OS) [ Time Frame: 36 months ]
    OS will be assessed for each cohort


Original Secondary Outcome: Same as current

Information By: Georgetown University

Dates:
Date Received: November 23, 2016
Date Started: December 2016
Date Completion: December 2019
Last Updated: November 28, 2016
Last Verified: November 2016