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MeningiomasPhase 2NCT02648997

An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma

A Phase 2 study testing Nivolumab - 240 mg, Ipilimumab - 1 mg/kg and Nivolumab - 480 mg in people with Meningiomas, run by Dana-Farber Cancer Institute at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in this study are nivolumab and ipilimumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Meningiomas
What is being tested?
Nivolumab - 240 mg, Ipilimumab - 1 mg/kg and Nivolumab - 480 mg
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Mar 2016to 1 Oct 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have histologically confirmed WHO grade I, II or III meningioma that is progressive or recurrent. Metastatic meningiomas are allowed. Participants with grade I tumors must have failed radiation therapy.
  • Prior therapy:
  • There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents.
  • Patients may have been treated with standard external beam radiation or radiosurgery in any combination, however, an interval of ≥ 12 weeks (84 days) must have elapsed from the completion of the radiation therapy to start of study therapy unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line).
  • In addition, there must be subsequent evidence of tumor progression after completion of radiation therapy (grade I tumors only)
  • An interval of ≥ 28 days and full recovery (no ongoing safety issues) from surgical resection
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  • An interval of ≥ 7 days from stereotactic biopsy;
  • For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas) or biologic therapies.
  • Participants must have recovered to grade ≤ 1 or pretreatment baseline from clinically significant adverse events related to prior therapy (exclusions include but are not limited to alopecia, laboratory values listed per inclusion criteria and lymphopenia);
  • Be 18 years of age on day of signing informed consent.
  • Have a Karnofsky performance status (KPS) ≥ 70 (Appendix A).
  • Participants must demonstrate adequate organ and marrow function as defined below (all screening labs to be performed within 14 days of treatment initiation):
  • White blood cell (WBC) ≥ 2000/mm3
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9 gm/dl
  • AST(SGOT)/ALT(SGPT) ≤ 3 x laboratory upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 X ULN OR
  • creatinine clearance (meas or calc) ≥ 60 mL/min for participants with creatinine levels > 1.5 X ULN
  • (GFR can be used in place of creatinine or creatinine clearance)
  • Total serum bilirubin ≤ 1.5 X ULN
  • (except participants with Gilbert's Syndrome, who can have a total bili < 5 X ULN)
  • Resting baseline oxygen saturation ≥ 92% at rest by pulse oximetry
  • MRI (or CT if MRI contraindicated) within 14 days prior to start of study drug. Corticosteroid dose must be stable or decreasing for at least 5 days prior to the scan. If steroids are added or the steroid dose is increased between the date of the screening MRI or CT scan and the start of treatment, a new baseline MRI or CT is required.
  • Ability to understand and the willingness to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study, including disease assessment by MRI (or CT), as confirmed by signing a written informed consent document.
  • For cohort 2, patients must be a candidate for external beam radiotherapy including either conventional fractionated conformal dosing or stereotactic radiosurgical boost dosing (participants may enroll if they are receiving radiotherapy or have completed it within 8 weeks of starting immunotherapy);
  • For cohort 2 patients who are undergoing fractionated conformal re-irradiation to a tumor site that has been previously irradiated, an interval of at least 6 months must have passed since they completed their prior irradiation to be eligible unless the current course of radiation is targeting a new area of tumor growth outside the 80% isodose line of the original radiation field as determined by the treating investigator.
  • The effects of nivolumab on the developing human fetus are unknown. For this reason:
  • Women of childbearing potential (WOCPB; defined in Section 3.4) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of starting study therapy;
  • Women must not be breastfeeding;
  • WOCPB must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study therapy plus 5 months after the last dose of Nivolumab.
  • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 7 months after the last dose of Nivolumab.
  • Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% per year when used consistently and correctly.
  • At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:
  • HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
  • Male condoms with spermicide
  • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena by WOCBP subjects or male subject's WOCBP partner. Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug
  • Progestogen only hormonal contraception associated with inhibition of ovulation
  • Intrauterine hormone-releasing system (IUS)
  • Nonhormonal IUDs, such as ParaGard
  • Tubal ligation
  • Vasectomy
  • Complete Abstinence - Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence.
  • LESS EFFECTIVE METHODS OF CONTRACEPTION
  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Vaginal sponge
  • Male Condom without spermicide
  • Progestin only pills by WOCBP subjects or male subject's WOCBP partner
  • Female Condom - A male and female condom must not be used together
  • UNACCEPTABLE METHODS OF CONTRACEPTION
  • Periodic abstinence (calendar, symptothermal, post-ovulation methods)
  • Withdrawal (coitus interruptus)
  • Spermicide only
  • Lactation amenorrhea method (LAM)
  • NOTE: Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP participants must still undergo pregnancy testing as described.

Who cannot join

  • Current or planned participation in a study of an investigational agent or using an investigational device.
  • Tumors that are primarily localized to the brainstem or spinal cord;
  • Evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans;
  • Prior Therapy:
  • Prior treatment with systemic immunosuppressive treatments, aside from systemic dexamethasone therapy for cerebral edema, such as methotrexate, chloroquine, azathioprine, etc. within 3 months of start of study therapy;
  • Prior treatment with interstitial brachytherapy within 6 months of start of study therapy;
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  • All patients: Previous treatment with PD-1 or PD-L1 directed therapy;
  • Cohort 2 patients: Previous treatment with CTLA-4 directed therapy;
  • Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment, or anticipation of need for major surgical procedure during the course of the study;
  • Minor surgical procedure (eg, stereotactic biopsy within 7 days of first study treatment; placement of a vascular access device within 2 days of first study treatment);
  • Other Meds:
  • Participants who are receiving any other investigational agents.
  • Immunosuppressive medications / steroids:
  • Subject must not require high dose systemic corticosteroids defined as dexamethasone > 4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks prior to Day 1of study therapy;
  • Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption).
  • Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents.
  • A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
  • Has received a live vaccine within 30 days prior to the first dose of study drug; seasonal influenza vaccination is permitted excluding the nasal spray formulation;
  • No concurrent treatment on another clinical trial. Supportive care trials or non- treatment trials, e.g. quality of life, are allowed;
  • Concomitant Medical Illnesses: Uncontrolled intercurrent illness, including-but not limited to:
  • Known additional malignancy that is progressing or requires active treatment within 3 years of start of study drug. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis;
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results examples include but are not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements;
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, conditions not expected to recur in the absence of an external trigger or resolved childhood asthma/atopy would be exceptions to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study;
  • Has an active infection requiring intravenous therapy;
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or detectable hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
  • Medical History:
  • History of intracranial abscess within 6 months prior to start of study therapy;
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
  • NOTE: HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Nivolumab. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • History of allergy to study drug components
  • History of severe hypersensitivity reaction to any monoclonal antibody;
  • Prisoners or participants who are involuntarily incarcerated;
  • Pregnant women are excluded from this study because Nivolumab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Nivolumab, breastfeeding should be discontinued if the mother is treated Nivolumab.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progressive/Recurrent Meningioma

This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in this study are nivolumab and ipilimumab.

Read the detailed description

This research is a Phase II clinical trial, which means it will test the safety and effectiveness of nivolumab alone (Cohort 1) or in combination with ipilimumab (Cohort 2). Both nivolumab and ipilimumab are antibodies (types of human protein) that work to stop tumor cells from growing and multiplying by immunotherapy. Immunotherapy is trying to have the body's own immune system work against tumor cells.

Nivolumab and ipilimumab have both been used in other research studies and information from those other research studies suggests that these interventions may help to stop Meningioma cells from growing.

Nivolumab is FDA approved to treat other types of cancers, but the FDA (the U.S. Food and Drug Administration) has not yet approved this intervention for this type of cancer. The FDA has not approved the combination of nivolumab and ipilimumab for your specific disease, but it has been approved for other uses.

Conditions
Meningiomas
Being tested
Nivolumab - 240 mg, Ipilimumab - 1 mg/kg, Nivolumab - 480 mg, Nivolumab - 3 mg/kg, External Beam RT
Keywords
Atypical Meningioma, Anaplastic Meningioma
Medical subject headings
Meningioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab - 240 mgDrug

    Also called Opdivo, BMS-936558, ONO-4538

    240 mg every 2 weeks

  • Ipilimumab - 1 mg/kgDrug

    Also called BMS-734016, MDX010, MDX-CTLA4

    1 mg/kg every 3 weeks

  • Nivolumab - 480 mgDrug

    Also called Opdivo, BMS-936558, ONO-4538

    480 mg once every 4 weeks

  • Nivolumab - 3 mg/kgDrug

    Also called Opdivo, BMS-936558, ONO-4538

    3 mg/kg every 3 weeks

  • External Beam RTRadiation

    IMRT, 3D-CRT, or proton-beam radiation therapy

  • Nivolumab - 1 mg/kgDrug

    Also called Opdivo, BMS-936558, ONO-4538

    1 mg/kg every 3 weeks

  • Ipilimumab - 3 mg/kgDrug

    Also called BMS-734016, MDX010, MDX-CTLA4

    3 mg/kg every 3 weeks

Study groups in NCT02648997
Study groupRoleWhat they receive
Cohort 1 (original cohort): Nivolumab MonotherapyExperimentalNivolumab monotherapy (240 mg every 2 weeks)
Receives: Drug: Nivolumab - 240 mg
Cohort 2 (Dose Level 0): Nivolumab in Combination with IpilimumabExperimental* External Beam RT (IMRT, 3D-CRT, or proton-beam radiation therapy) * Followed by 4 cycles of Nivolumab (1 mg/kg every 3 weeks) + Ipilimumab (3 mg/kg every 3 weeks) * Followed by Nivolumab monotherapy (480 mg every 4 weeks).
Receives: Drug: Nivolumab - 240 mg; Drug: Nivolumab - 480 mg; Radiation: External Beam RT; Drug: Nivolumab - 1 mg/kg; Drug: Ipilimumab - 3 mg/kg
Cohort 2 (Dose Level 0A): Nivolumab in Combination with IpilimumabExperimental* External Beam RT (IMRT, 3D-CRT, or proton-beam radiation therapy) * Followed by 4 cycles of Nivolumab (3 mg/kg every 3 weeks) + Ipilimumab (1 mg/kg every 3 weeks) * Followed by Nivolumab monotherapy (480 mg every 4 weeks).
Receives: Drug: Nivolumab - 240 mg; Drug: Ipilimumab - 1 mg/kg; Drug: Nivolumab - 480 mg; Drug: Nivolumab - 3 mg/kg; Radiation: External Beam RT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Without Disease Progression At Six Months Following Initiation Of Study Therapy

    To evaluate the anti-tumor activity for single-agent nivolumab (cohort 1) or nivolumab plus ipilimumab following radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma.

    Measured: 6 months

Secondary outcomes (4)

  1. Both Cohorts: Median Progression-Free Survival

    To evaluate additional measures of anti-tumor activity of single-agent nivolumab (cohort 1) and nivolumab plus ipilimumab after radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma

    Measured: 2 years

  2. Both Cohorts: Median Overall Survival

    To evaluate additional measures of anti-tumor activity of single-agent nivolumab (cohort 1) and nivolumab plus ipilimumab after radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma

    Measured: 2 years

  3. Both Cohorts: Objective Radiologic Response Rate

    To evaluate additional measures of anti-tumor activity of single-agent nivolumab (cohort 1) and nivolumab plus ipilimumab after radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma

    Measured: 2 years

  4. Both Cohorts: Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0.

    1.2.1 To evaluate the safety and tolerability of single-agent nivolumab (cohort 1) and nivolumab plus ipilimumab after radiation therapy (cohort 2) among patients with recurrent/progressive grade I, II or III meningioma

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2016 (estimated)
  2. Study startMar 2016
  3. Primary completion1 Dec 2024
  4. Study completion1 Oct 2026 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
After completion of accrual to Cohort 1, we opened accrual to Cohort 2.
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02648997
Sponsor's protocol ID
15-490
Other IDs
CA209-324
Status last verified
Jun 2026
First submitted
5 Jan 2016
Last updated
10 Jul 2026
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab - 240 mg, Ipilimumab - 1 mg/kg and Nivolumab - 480 mg in people with Meningiomas, run by Dana-Farber Cancer Institute 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 57 inclusion and 35 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: under way, not looking for participants, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants Without Disease Progression At Six Months Following Initiation Of Study Therapy (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02648997.

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.

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