Atypical MeningiomaPhase 2NCT03016091
A Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma
A Phase 2 study testing Pembrolizumab in people with Atypical Meningioma and Anaplastic Meningioma, run by Rabin Medical Center at 2 sites in Israel.
Trial summary
A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Atypical Meningioma, Anaplastic Meningioma, Hemangiopericytoma
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesIsrael
- Study dates
- 1 Jan 2018to 1 Dec 2022
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Histologically, previously proven, grade II or III meningioma, HPC or classic radiographic features of a recurrent surgically inaccessible atypical or anaplastic meningioma.
- All patients would have to have recurrence despite radiotherapy, unless radiotherapy is contraindicated.
- No limit on the number of prior surgeries, radiation or radiosurgery treatments.
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- No limit on prior systemic therapies - chemotherapy or biological agents.
- Patients who received stereotactic radiosurgery (SRS) are eligible without histologic documentation of recurrence if at least 6 months have passed from previous SRS treatment, and preferably, but not necessarily a 2-fluoro-2-deoxy-D-glucose PET imaging demonstrated hypermetabolism.
- KPS≥50%
- At least 4 weeks since any prior therapy.
- Life expectancy of at least 4 months.
- Dexamethasone use will be allowed up to a dose of 2mg per day. Steroids dose should be reduced or stopped 7 days prior to treatment with study drug.
- Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
- Table 1 Adequate Organ Function Laboratory Values
- Hematological Absolute neutrophil count (ANC)≥1,500 /mcL Platelets≥100,000 / mcL Hemoglobin≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of normal (ULN) OR
- ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR
- ≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
- Activated Partial Thromboplastin Time (aPTT)≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants a Creatinine clearance should be calculated per institutional standard.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
- Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients who are steroid dependent and cannot reduce the dexamethasone dose to a maximal dose of 2mg per day.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
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- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of, or any evidence of active, non-infectious pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of planned start of study therapy.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma
A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma
Read the detailed description
This is a multicenter, prospective, single arm, open label, interventional study. The goal of this study, is to evaluate feasibility and efficacy of pembrolizumab for the treatment of recurrent or progressive meningioma (WHO grades II-III) or hemangiopericytoma (HPC). All patients will receive IV pembrolizumab, at a dose of 200mg, every 3 weeks. Patients will be treated until disease progression or intolerable toxicity. Treatment can be stopped after one year of treatment in case of stable disease or completer response, with re-initiation of treatment upon progression. Expression of PD1 and PD-L1 will be tested, on tumor cells, using IHC staining on biopsy material obtained from previous surgeries.
All patients will have a baseline neurologic and clinical exam, MRI scan, a brain dedicated CT-PET scan, a baseline cognitive exam and QOL assessment with a dedicated questionnaire. Patients will have a clinical and neurological exam every treatment cycle. MRI scan will be repeated after 2 months from the beginning of the trial drug administration and then every 2-3 months. There are no designated and specific criteria for response assessment in the treatment of meningioma. Therefore, response evaluation will be made using the RECIST 1.1 criteria, as used for solid tumors. The trial will allow the continuation of pembrolizumab in case of stable or improved clinical response, when pseudo-progression is suspected in the MRI. In addition, response assessment will also be made according to the RANO criteria, as used for high grade glioma. This will be compared to the RECIST evaluation, but will not be used for treatment decision making.
- Being tested
- Pembrolizumab
- Medical subject headings
- Meningioma, Hemangiopericytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
anti PD-L1
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | IV Pembrolizumab 200mg, given every 3 weeks until disease progression or intolerable toxicity Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
6 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 6 months after starting treatment.
To determine the 6 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.
Measured: 6 months after starting treatment
Progression Free Survival (PFS)
12 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 12 months after starting treatment.
To determine the 12 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.
Measured: 12 months after starting treatment
Secondary outcomes (2)
Overall Survival (OS)
Overall survival (OS) is a term used in reference to treatments for cancer. It refers to the time which begins at diagnosis and up to the time of death.
Measured: from date of diagnosis until date of death from any cause
Overall Progression Free Survival (PFS)
To determine the overall progression free survival (PFS) rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.
Measured: From the initiation of treatment to the occurrence of disease progression or death.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2017 (estimated)
- Study start1 Jan 2018
- Primary completion1 Jul 2022
- Study completion1 Dec 2022
Why it stopped: Slow accrural, dismal results
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atypical MeningiomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03016091
- Sponsor's protocol ID
- MK-3475-415
- Status last verified
- Jan 2018
- First submitted
- 22 Dec 2016
- Last updated
- 18 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma
- ClinicalTrials.gov ID
- NCT03016091
- Acronym / sponsor ID
- MK-3475-415
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrural, dismal results
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 10 Jan 2017 (estimated)
- Results
- Posted 22 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma
Detailed description
This is a multicenter, prospective, single arm, open label, interventional study. The goal of this study, is to evaluate feasibility and efficacy of pembrolizumab for the treatment of recurrent or progressive meningioma (WHO grades II-III) or hemangiopericytoma (HPC). All patients will receive IV pembrolizumab, at a dose of 200mg, every 3 weeks. Patients will be treated until disease progression or intolerable toxicity. Treatment can be stopped after one year of treatment in case of stable disease or completer response, with re-initiation of treatment upon progression. Expression of PD1 and PD-L1 will be tested, on tumor cells, using IHC staining on biopsy material obtained from previous surgeries.
All patients will have a baseline neurologic and clinical exam, MRI scan, a brain dedicated CT-PET scan, a baseline cognitive exam and QOL assessment with a dedicated questionnaire. Patients will have a clinical and neurological exam every treatment cycle. MRI scan will be repeated after 2 months from the beginning of the trial drug administration and then every 2-3 months. There are no designated and specific criteria for response assessment in the treatment of meningioma. Therefore, response evaluation will be made using the RECIST 1.1 criteria, as used for solid tumors. The trial will allow the continuation of pembrolizumab in case of stable or improved clinical response, when pseudo-progression is suspected in the MRI. In addition, response assessment will also be made according to the RANO criteria, as used for high grade glioma. This will be compared to the RECIST evaluation, but will not be used for treatment decision making.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: PembrolizumabIV Pembrolizumab 200mg, given every 3 weeks until disease progression or intolerable toxicity |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Histologically, previously proven, grade II or III meningioma, HPC or classic radiographic features of a recurrent surgically inaccessible atypical or anaplastic meningioma.
- All patients would have to have recurrence despite radiotherapy, unless radiotherapy is contraindicated.
Key exclusion criteria (21 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients who are steroid dependent and cannot reduce the dexamethasone dose to a maximal dose of 2mg per day.
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
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 |
|---|---|---|
| Pembrolizumabanti PD-L1 | Drug | Arm 1 |
Primary outcome
Progression Free Survival (PFS)
Time frame: 6 months after starting treatment
6 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 6 months after starting treatment. To determine the 6 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.
Progression Free Survival (PFS)
Time frame: 12 months after starting treatment
12 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 12 months after starting treatment. To determine the 12 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.
2 secondary outcomes
Overall Survival (OS)
Time frame: from date of diagnosis until date of death from any cause
Overall Progression Free Survival (PFS)
Time frame: From the initiation of treatment to the occurrence of disease progression or death.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Atypical Meningioma and Anaplastic Meningioma, run by Rabin Medical Center at 2 sites in Israel.
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 24 inclusion and 21 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: stopped early, as of the sponsor's last update on 18 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. 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 22 Jan 2025). 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?
Progression Free Survival (PFS) (time frame: 6 months after starting treatment). The study lists 2 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 18 Feb 2025.