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

NCT ID: NCT04465643

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-08
• Study Completion Date: 2025-07-30

Brief Summary

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.

Conditions

Nerve Sheath Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunotherapy with Nivolumab and Ipilimumab

Nivolumab 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

Group Type: OTHER

Nivolumab

Intervention Type: DRUG

Nivolumab 4.5 mg/kg Q3W x 2

Ipilimumab

Intervention Type: DRUG

Ipilimumab 1 mg/kg Q3W x 2

Interventions

Nivolumab

Nivolumab 4.5 mg/kg Q3W x 2

Intervention Type: DRUG

Ipilimumab

Ipilimumab 1 mg/kg Q3W x 2

Intervention Type: DRUG

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.)

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

Cancer Research and Biostatistics Clinical Trials Consortium

NETWORK

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaishri Blakeley, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Medical Institution

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

IRB00215437

Identifier Type: OTHER

Identifier Source: secondary_id

W81XWH-22-1-0580

Identifier Type: OTHER

Identifier Source: secondary_id

J20112

Identifier Type: -

Identifier Source: org_study_id