Clinical Trials Search
Clinical Trial 18068
Cancer Type: Neurologic Oncology
Interventions:BMS-936558 (Nivolumab); Ipilimumab; Nivolumab; Yervoy (Ipilimumab)
Study Type: Treatment
Phase of Study: Phase II
- Peter Forsyth
A Multi-Center Phase 2 Open-Label Study to Evaluate Safety and Efficacy in Subjects with Melanoma Metastatic to the Brain treated with Nivolumab in Combination with Ipilimumab followed by Nivolumab Monotherapy
The purpose of this study is to give participants an opportunity to receive treatment with an investigational drug called nivolumab (also known as BMS-936558) in combination with ipilimumab (YERVOY) followed by nivolumab monotherapy.
Primary Objective: * To assess the CNS clinical benefit rate (CBR, defined as complete response [CR] + partial response [PR] + stable disease [SD] > 6 months per protocol defined response criteria) in subjects with melanoma metastatic to the brain treated with nivolumab combined with ipilimumab followed by nivolumab monotherapy. Secondary Objectives: * To assess the extracranial clinical benefit rate defined as CR+PR+SD >6 months (per RECIST 1.1 criteria). * To assess the global clinical benefit rate (CBR), defined as CR+PR+SD >6 months CNS plus extracranial(per RECIST 1.1 with modifications). * To assess the CNS, extracranial, and global CBR per irRC (immune-related Response Criteria). * To assess overall survival (OS). * To evaluate the CNS-specific safety and tolerability of the combination regimen in patients with or without stereotactic radiotherapy (SRT) received prior to study entry, or on study. Exploratory Objectives: * To evaluate the overall safety and tolerability of the combination regimen in patients with or without stereotactic radiotherapy (SRT) received prior to study entry, or on study. * To evaluate association between baseline pathologic features of primary cutaneous melanoma (e.g., regression, ulceration, pattern and components of immune infiltrate) and CBR endpoints. * To explore potential biomarkers associated with clinical response to nivolumab combined with ipilimumab by analyzing tumor tissue specimens for proteins including, but not limited to, PD-1, PD-L1, and other markers related to immune cell populations involved in regulating immune responses in comparison to clinical outcomes. * To evaluate association between BRAF/NRAS mutation status and response endpoints. * To compare tissue biomarker profiles between paired tissues from extracranial and brain metastases from individual patients, where available; if possible this analysis will also be applied for sample sets that include a primary, an extracranial metastasis and a brain metastasis from the same patient. * To assess peripheral blood immune cell subpopulations (which may include but is not limited to CD4+ Tcell, CD8+ T-cell, Treg, NK, B-cell, MDSC, activated T-cells, memory/exhausted T-cells) and serum soluble factors with changes in post-treatment profiles as they relate to clinical endpoints and/or the occurrence of adverse events. * To assess the effects of natural genetic variation (SNPs) in select genes including, but not limited to, PD-1, PD-L1, PD-L2, and CTLA-4 on clinical endpoints and/or on the occurrence of adverse events. * To estimate the incidence of MRI-defined brain edema, hemorrhage and increase in tumor size before regression (pseudoprogression) in the brain metastases and to evaluate any association with the onset and/or clinical benefit rate (CR+ PR+SD >6 mo.) observed in the brain or non-CNS. * To compare computer-assisted tumor volume from three dimensional (3D) MRI to bi-dimensional measures with respect to absolute values and percent change from baseline.