Nerve Sheath TumorsPhase 1NCT04465643
Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor
A Phase 1 study testing Nivolumab and Ipilimumab in people with Nerve Sheath Tumors, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 100 years
- Conditions the study is for
- Nerve Sheath Tumors
- What is being tested?
- Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2021to 30 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Medical Institution
Baltimore, Maryland, 21287
About this study
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
- Being tested
- Nivolumab, Ipilimumab
- Medical subject headings
- Nerve Sheath Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Nivolumab 4.5 mg/kg Q3W x 2
IpilimumabDrug
Ipilimumab 1 mg/kg Q3W x 2
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy with Nivolumab and Ipilimumab | Other | 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 Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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
Measured: Up to 8 weeks
Secondary outcomes (5)
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)
Measured: Up to 2 years
Objective response rate (ORR)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 6, 4 months, and 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2020
- Study start8 Jun 2021
- Primary completion30 Jul 2025
- Study completion30 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nerve Sheath TumorsStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Congressionally Directed Medical Research Programs, Cancer Research and Biostatistics Clinical Trials Consortium
- Responsible party
- Sponsor
- Investigators
- Jaishri Blakeley, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04465643
- Sponsor's protocol ID
- J20112
- Other IDs
- IRB00215437, W81XWH-22-1-0580
- Status last verified
- Jul 2026
- First submitted
- 7 Jul 2020
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Nivolumab Plus Ipilimumab for Newly Diagnosed Malignant Peripheral Nerve Sheath Tumor
- ClinicalTrials.gov ID
- NCT04465643
- Acronym / sponsor ID
- J20112
- Conditions
- Nerve Sheath Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Congressionally Directed Medical Research Programs, Cancer Research and Biostatistics Clinical Trials Consortium
- Study start
- 8 Jun 2021 (actual)
- Primary completion
- 30 Jul 2025 (actual)
- Study completion
- 30 Jul 2025 (actual)
- First posted
- 10 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy with Nivolumab and Ipilimumab | Other | Drug: Nivolumab, Drug: IpilimumabNivolumab 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 |
Who may qualify
- Ages
- 12 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabNivolumab 4.5 mg/kg Q3W x 2 | Drug | Immunotherapy with Nivolumab and Ipilimumab |
| IpilimumabIpilimumab 1 mg/kg Q3W x 2 | Drug | Immunotherapy with Nivolumab and Ipilimumab |
Primary outcome
Safety of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events
Time frame: Up to 2 years
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).
Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events
Time frame: Up to 2 years
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).
Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)
Time frame: Up to 2 years
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).
Feasibility of combination nivolumab and ipilimumab as assessed by number of participants who start standard of care within standard treatment window
Time frame: Up to 8 weeks
Number of participants who start standard of care treatment within 8 week
5 secondary outcomes
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
Objective response rate (ORR)
Time frame: Up to 2 years.
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaishri Blakeley, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab and Ipilimumab in people with Nerve Sheath Tumors, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of combination nivolumab and ipilimumab as assessed by number of participants who experience adverse events (time frame: Up to 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.