The purpose of the study is to evaluate safety and feasibility of neoadjuvant nivolumab plus ipilimumab prior to standard therapy (surgery, chemotherapy or radiation therapy) in patients with Neurofibromatosis Type 1 (NF1) and newly diagnosed pre-malignant and malignant peripheral nerve sheath tumors (MPNST) for whom surgery for resection of tumor is indicated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Nivolumab 4.5 mg/kg Q3W x 2
Ipilimumab 1 mg/kg Q3W x 2
Johns Hopkins Medical Institution
Baltimore, Maryland, United States
Safety of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Time frame: Up to 2 years
Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Time frame: Up to 2 years
Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)
Maximum tolerated dose will be determined by the maximum dose at which the least number of participants experience dose-limiting toxicity. The dose limiting toxicity is defined using the Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: Up to 2 years
Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who start standard of care within standard treatment window
Number of participants who start standard of care treatment within 8 week
Time frame: Up to 8 weeks
Safety as assessed by number of treatment-emergent adverse events in patients on combination nivolumab and ipilimumab with NF1, standard low, or high grade MPNST therapy
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)
Time frame: Up to 2 years
Objective response rate (ORR)
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Proportion of participants with measurable disease at baseline and have been re-evaluated after at least 1 cycle of therapy with observed reduction in tumor burden as defined by RECIST and iRECIST criteria after 2 doses of nivolumab and ipilimumab.
Time frame: Up to 2 years.
Change in pain levels in relation to target tumor as assessed by the Numeric Rating Scale
Evaluate pain levels in participants related to target tumor via the Numeric Rating Scale. Assessment to be performed at baseline, Week 6, 4 months, and 8 months via numeric grading scale (0 through 10) recorded by participant via survey in order to determine an improvement or worsening of pain throughout treatment. Lower scores indicate no pain or decreased levels of pain while higher score indicate increased levels of pain.
Time frame: Baseline, Week 6, 4 months, and 8 months
Change in pain levels in relation to target tumor as assessed by the Pain Interference Index
Evaluate pain in participants related to target tumor via the Pain Interference Index (6-24 years). Assessment to be performed at baseline, Week 6, 4 months, and 8 months via numeric grading scale (0 through 6) recorded by participant via survey In order to determine an improvement or worsening of pain throughout treatment. Lower scores indicate no interference or decreased levels of interference in every day life while higher scores indicate increased interference in ever day life.
Time frame: Baseline, Week 6, 4 months, and 8 months
Change in pain levels in relation to target tumor as assessed by the Patient-Reported Outcome Measurement Information System
Evaluate pain in participants related to target tumor via the Patient-Reported Outcome Measurement Information System (PROMIS). Assessment to be performed at at baseline, Week 6, 4 months, and 8 months via numeric grading scale (1 through 5) recorded by participant via survey in order to determine an improvement or worsening of pain throughout treatment. Higher scores indicate no to low difficulty in mobility while lower scores indicate increased difficulty or inability in mobility.
Time frame: Baseline, Week 6, 4 months, and 8 months