Clinical Trials /

Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor

NCT04465643

Description:

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.

Related Conditions:
  • Low Grade Glioma
  • Malignant Peripheral Nerve Sheath Tumor
  • Optic Nerve Glioma
  • Plexiform Neurofibroma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor
  • Official Title: Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor

Clinical Trial IDs

  • ORG STUDY ID: CA209-8WM
  • NCT ID: NCT04465643

Conditions

  • Nerve Sheath Tumors

Interventions

DrugSynonymsArms
NivolumabImmunotherapy with Nivolumab and Ipilimumab
IpilimumabImmunotherapy with Nivolumab and Ipilimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Immunotherapy with Nivolumab and IpilimumabOtherNivolumab 4.5 mg/kg every 3 weeks (Q3W) x 2 Ipilimumab 1 mg/kg Q3W x 2 Nivolumab monotherapy 4.5mg/kg Q3W concurrent with standard therapy Nivolumab monotherapy should be held for at least 2 weeks before and 2 weeks after surgery
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of atypical neurofibromatous neoplasms of uncertain
             biologic potential (ANNUBP), low grade malignant peripheral nerve sheath tumor (MPNST)
             or high grade MPNST in accordance with the Miettinen et al diagnostic criteria via
             biopsy

          -  Plexiform neurofibroma or other tumors such as optic pathway glioma, other low-grade
             glioma or other neoplasm in addition to the ANNUBP, low grade MPNST or high grade
             MPNST that is stable (has not required treatment in the last 12 months and is not
             anticipated to need treatment in the next 12 months)

          -  Measureable disease by RECIST criteria in at least one site.

          -  Karnofsky Performance Scale ≥ 60%

          -  No contraindications for Nivolumab or Ipilimumab

          -  Normal organ and marrow function on routine laboratory tests

          -  Evidence of post-menopausal status or negative urinary/serum pregnancy test for female
             pre-menopausal subjects. Women will be considered post-menopausal if they have been
             amenorrheic for 12 months without an alternative medical cause

          -  Ability to understand and willingness of sign consent form

          -  Willingness to comply with the protocol for the duration of the study

        Exclusion Criteria:

          -  Chemotherapy or other investigational agent for the current episode of newly diagnosed
             atypical neurofibroma or MPNST

          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody

          -  Known allergy to compounds of similar chemical or biologic composition to Nivolumab or
             Ipilimumab

          -  Pregnant or breastfeeding women

          -  Known history of Human Immunodeficiency Virus

          -  Active infection requiring therapy, including known positive tests for Hepatitis B
             surface antigen or Hepatitis C ribonucleic acid (RNA)

          -  Active autoimmune disease, history of autoimmune disease or history of syndrome that
             required systemic steroids or immunosuppressive medications, e.g. organ, tissue, or
             allogenic hematopoietic stem cell transplant (HSCT) recipients. Exceptions include
             those with resolved childhood asthma/atopy. Subjects with asthma who require
             intermittent use of bronchodilators (such as albuterol) will not be excluded from this
             study. Subjects are also permitted to enroll if they have vitiligo, type I diabetes
             mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
             replacement, psoriasis not requiring systemic treatment, or conditions not expected to
             recur in the absence of an external trigger

          -  A condition requiring systemic treatment with either corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days of study
             drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg
             daily prednisone equivalents are permitted in the absence of active autoimmune
             disease.

          -  Use of any vaccines against infectious diseases (e.g. varicella, influenza, etc.) up
             to 4 weeks (28 days) before receiving nivolumab and ipilimumab.

          -  Prisoners or subjects who are compulsorily detained for treatment of either a
             psychiatric or physical (e.g. infectious disease) illness

          -  Prior radiation doses equivalent to, or greater than, 8000 centigray (cGy) to the
             target lesions at 200 cGy fractions at any time point

          -  Any radiation to the the target lesions within 6 months of enrollment

          -  Other concurrent severe and/or uncontrolled medical disease, which could compromise
             participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension,
             severe infection, severe malnutrition, chronic liver or renal disease, active upper GI
             tract ulceration, congestive heart failure, etc.)
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events
Time Frame:Up to 2 years
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure: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
Time Frame:Up to 2 years
Safety Issue:
Description: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)
Measure:Objective response rate (ORR)
Time Frame:Up to 2 years.
Safety Issue:
Description: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.
Measure:Change in pain levels in relation to target tumor as assessed by the Numeric Rating Scale
Time Frame:Baseline, Week 6, 4 months, and 8 months
Safety Issue:
Description: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.
Measure:Change in pain levels in relation to target tumor as assessed by the Pain Interference Index
Time Frame:Baseline, Week 6, 4 months, and 8 months
Safety Issue:
Description: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.
Measure:Change in pain levels in relation to target tumor as assessed by the Patient-Reported Outcome Measurement Information System
Time Frame:Baseline, Week 6, 4 months, and 8 months
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

July 7, 2020