Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Meningioma

Disease Attributes

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5. Patients undergo brain MRI and blood sample collection throughout the study. Patients may also undergo ECHO as clinically indicated.

Patients receive nivolumab IV over 30 minutes every 2 weeks for 12 doses (6 months) and then every 4 weeks for additional 6 months. Patients also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 6 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5. Patients undergo brain MRI and blood sample collection throughout the study. Patients may also undergo ECHO as clinically indicated.

Biospecimen Collection

Echocardiography

Magnetic Resonance Imaging

Undergo multi-fraction stereotactic radiosurgery

Stereotactic Radiosurgery

Site Public Contact

Aaron B. Simon

Douglas E. Ney

Gregory A. Azzam

Sani H. Kizilbash

David Akhavan

Lawrence R. Kleinberg

Jiayi Huang

Aya Haggiagi

Simon Khagi

Megan Mantica

Joe S. Mendez

David Schiff

This phase I/II trial studies the side effects and best dose of nivolumab when given together with multi-fraction stereotactic radiosurgery and to see how well they work with or without ipilimumab in treating patients with grade II-III meningioma that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Giving nivolumab and multi-fraction stereotactic radiosurgery with or without ipilimumab may work better in treating patients with grade II-III meningioma.

PRIMARY OBJECTIVES:

I. To evaluate the maximum tolerated combination and safety profile of multi-fraction radiosurgery with concurrent nivolumab plus or minus ipilimumab for recurrent radiation-relapsed high-grade meningioma. (Phase I) II. To evaluate the objective response rate (ORR) of multi-fraction radiosurgery with concurrent nivolumab plus or minus ipilimumab for recurrent radiation-relapsed high-grade meningioma. (Phase II)

SECONDARY OBJECTIVE:

I. To evaluate duration of overall response, progression-free survival (PFS) and overall survival (OS) of recurrent radiation-relapsed high-grade meningioma patients treated with the combination of multi-fraction radiosurgery and nivolumab plus or minus ipilimumab.

CORRELATIVE OBJECTIVES:

I. To analyze the immunophenotype changes of peripheral T-cells during the treatment with multi-fraction radiosurgery in combination with nivolumab plus or minus ipilimumab.

II. To perform molecular profiling assays on pretreatment/baseline archival tumor, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to IIa. Identify potential predictive and prognostic biomarkers (such as neoantigen signature or mutation burden) beyond any genomic alteration by which treatment may be assigned.

IIb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.

III. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.

IV. To bank formalin-fixed, paraffin-embedded (FFPE) tissue, blood (for cell-free DNA analysis), and nucleic acids obtained from patients at the National Cancer Institute Early-Phase and Experimental Clinical Trials Biospecimen Bank (EET Biobank).

OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study. Patients are randomized to 1 of 2 cohorts.

COHORT A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5.

COHORT B: Patients receive nivolumab IV over 30 minutes every 2 weeks for 12 doses (6 months) and then every 4 weeks for additional 6 months. Patients also receive ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 6 weeks for 4 doses in the absence of disease progression or unacceptable toxicity. Patients undergo multi-fraction stereotactic radiosurgery on days 1, 3, and 5.

Patients undergo brain magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo echocardiogram (ECHO) as clinically indicated.

After completion of study treatment, patients are followed up for 100 days.

Nivolumab and Multi-fraction Stereotactic Radiosurgery With or Without Ipilimumab in Treating Patients With Recurrent Grade II-III Meningioma

A Phase I/II Study of Nivolumab Plus or Minus Ipilimumab in Combination With Multi-Fraction Stereotactic Radiosurgery for Recurrent High-Grade Radiation-Relapsed Meningioma

Will be explored by comparing the differences in theses biomarkers between responders versus non-responders using t-test or Mann-Whitney rank-sum test as appropriate. Permutation test will be used to determine whether the observed difference is larger than might be expected by chance, while the null distribution of test statistics will be generated using 10,000 permutation samples where the response status will be randomly re-shuffled. The observed test statistics will be compared to the null distributions. For each outcome, the permuted p-value will be the fraction of permuted samples that resulted in a small statistic than the original sample.

Will be evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The number and percentage of subjects experiencing each type of adverse event will be tabulated by severity, and relationship to treatment. If appropriate, confidence intervals will be used to characterize the precision of the estimate. A complete listing of adverse events will also be tabulated, and will provide details including severity, relationship to treatment, onset, duration, and outcome. Laboratory data measured on a continuous scale will be characterized by summary statistics (mean and standard deviation).

Will include either complete response or partial response as assessed on magnetic resonance imaging (MRI) per the modified Macdonald Criteria. 80% confidence intervals will be calculated.

80% confidence intervals will be assessed using Kaplan-Meier product limit methods.

Each T-cell subset will be quantified as a percentage of the overall T-cell population by normalizing to CD3+ cells. Linear mixed model for repeated measurement data will be used to assess the change over time as well as the differences between subgroups (e.g., responders vs. non-responders) for immunogenicity and other biomarkers (i.e., frequency of CD8+Ki67+PD1+ T-cells, etc.). Receiver operating characteristic (ROC) curves will also be used to assess the overall predictive ability and to explore the optimal cut-off points for baseline biomarkers to differentiate responders versus non-responders.

National Cancer Institute (NCI)

Disease Progression

Gastrointestinal Agents

Micronutrients

Carboxymethylcellulose Sodium

Silicon

Participants will self-administer cabozantinib 60 mg at the same time daily by mouth on a continuous 28-day schedule. Participants will continue to take this medication as long as they are deriving benefit from it without significant treatment-related toxicities.

Cabozantinib tablets are supplied as film coated tablets containing cabozantinib malate equivalent to 20 mg and 60 mg of cabozantinib and contain microcrystalline cellulose, lactose anhydrous, hydroxypropyl cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and Opadry® yellow. The 60 mg tablets are oval and the 20 mg tablets are round. Doses of 40 mg will comprise two 20-mg tablets.

Cabozantinib

Rupesh R Kotecha, M.D.

Anais Vega

Rupesh R Kotecha, MD

Yazmin Odia, MD

Yazmin Odia, M.D.

A Phase II Study of Cabozantinib for Patients with Recurrent or Progressive Meningioma

Cabozantinib for Patients With Recurrent or Progressive Meningioma

A Phase II Study of Cabozantinib for Patients With Recurrent or Progressive Meningioma

Proportion of participants who from start of treatment to 6-months are free from objective tumor progression or death from any cause.

Proportion of participants with confirmed complete response (CR) or partial response (PR) assessed by Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria, relative to the total population of patients enrolled who initiate therapy.

Overall Survival (OS): duration of time from start of treatment until death from any cause. Patients lost-to follow up will be censored at last valid assessment.

Proportion of participants who develop adverse events assessed by CTCAE v5.0 criteria.

QOL will be measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) Version 4. The FACT-Br questionnaire is a 23-item survey, participants then rate each item on a Likert scale from 0 "not at all" to 4 "very much", and overall, higher ratings are suggestive of better quality of life.

QOL will be assessed at the baseline, day 1 of every cycle (treatment days, every 4 weeks on 28-day cycle, and every 6 weeks on 42-day cycle).

Exelixis

Baptist Health South Florida

Lutetium Lu 177 dotatate

Radiopharmaceuticals

Patients receive gallium Ga 68-DOTATATE IV and undergo a PET/MRI or PET/CT before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI on study and during follow-up, as well as blood sample collection and possible SEPCT/CT dosimetry on study.

Gallium Ga 68-DOTATATE

Lutetium Lu 177 Dotatate

Positron Emission Tomography

Questionnaire Administration

Computed Tomography

Single Photon Emission Computed Tomography

Clinical Trials Referral Office

Kenneth W. Merrell, M.D.

This phase II trial studies how well lutathera works in treating patients with meningioma that cannot be treated with surgery (inoperable) and is growing, spreading, or getting worse (progressive) after external beam radiation therapy. Lutathera is a radioactive drug administered in the vein that is designed to target and kill tumor cells. The goal of this study is to determine whether this drug is safe and effective in treating meningiomas that progress after radiation treatment. WHO Grade I and Cohort WHO II/III cohorts will be evaluated.

PRIMARY OBJECTIVES:

I. To estimate the efficacy of lutetium Lu 177 dotatate (LUTATHERA) treatment in patients with recurrent grade 1 meningioma as measured by 6-month progression-free survival (PFS) rate.

II. To estimate the efficacy of LUTATHERA treatment in patients with recurrent grade 2 or 3 meningioma as measured by 6-month PFS rate.

SECONDARY OBJECTIVES:

I. To determine the overall survival (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

II. To determine the progression-free survival (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

III. To determine the toxicity of LUTATHERA treatment in patients with recurrent meningioma.

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess the impact of treatment on the patient's quality of life (QOL) using the Promise-10, Brief Fatigue Inventory (BFI), and Mayo Patient Survey National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) Brain Symptom Index Questionnaire-24 (FBrSI-24) (version 2) instruments.

II. To compare the response assessment between standard of care brain magnetic resonance imaging (MRI) and gallium Ga 68-DOTATATE (68Ga-DOTATATE) positron emission tomography (PET) imaging.

III. To determine the best objective response (Macdonald criteria) of patients with recurrent meningioma during or after treatment of LUTATHERA.

IV. To determine the duration of local control with death as a competing risk (by grade cohort) of patients with recurrent meningioma during or after treatment of LUTATHERA.

V. To perform a quantitative dosimetric analysis of radiation dose delivered with lutathera:

Va. To determine intratherapeutic dosimetry for the target meningioma; Vb. To correlate treatment response of lutathera with target dose received; Vc. To determine intratherapeutic dosimetry for kidneys and other abdominal organs.

OUTLINE:

Patients receive gallium Ga 68-DOTATATE intravenously (IV) and undergo a PET/MRI or PET/computed tomography (CT) before cycles 1 and 4. Patients then receive lutetium Lu 177 dotatate IV over 30-40 minutes. Treatment repeats every 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI on study and during follow-up, as well as blood sample collection and possible single photon emission computed tomography (SPECT)/CT dosimetry on study.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 5 years.

Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy

A Prospective, Phase II Study of Lutetium Lu 177 Dotatate (LUTATHERA®) in Patients With Inoperable, Progressive Meningioma After External Beam Radiation Therapy

QOL will be measured using the standard survey series for this population of patients, and QOL trajectory over time will be examined. The survey series includes Promise-10, Brief Fatigue Inventory, and Mayo Patient Survey National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Brain Symptom Index Questionnaire-24 (version 2). The main QOL impact will be measured with differences from baseline to 6, 12 and 24 months in patient reported outcomes via the symptom scales from the above surveys. All other QOL analyses will be exploratory and may include change from baseline to all time points using t-test and generalized linear models to test for changes at each time point and non-zero slopes, respectfully. No formal comparisons will be made among the cohorts.

Will be defined as a best objective response of stable disease, partial or complete response to treatment as determined by Macdonald Criteria. The proportion of patients who have achieved local control will be summarized by cohort and 95% confidence intervals calculated according to the methods described in Clopper-Pearson. No formal comparison will be made among the cohorts.

The distribution of local control and survival without progression as a competing risk model will be constructed using Kaplan-Meier estimates. No formal comparisons will be made amongst the cohorts.

Will be determined by Macdonald Criteria. The proportion of patients in each response category will be summarized by cohort and 95% confidence intervals calculated according to the methods described in Clopper-Pearson. No formal comparison will be made among the cohorts.

The response rate determined by volumetric analysis will be estimated for each cohort with proportion of patients who achieve complete response/partial response deemed by volumetric analysis. The 90% two-sided confidence intervals will be calculated according to approach of Clopper-Pearson. No formal comparison will be made among the cohorts.

Will be defined as the number of evaluable patients not having progressive disease or death within six months of the first day of treatment divided by the total number of evaluable patients. The proportion of successes in each cohort will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper-Pearson. There will be no formal comparison of rates among the two different grade cohorts of patients.

The distribution of survival time for both cohorts will be estimated using the method of Kaplan-Meier. No formal comparison will be made among the cohorts.

The distribution of time to progression will be estimated using the method of Kaplan-Meier (Kaplan et. al 1958). No formal comparison will be made among the cohorts.

Will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Mayo Clinic

Antisickling Agents

Anti-Infective Agents

Bevacizumab

Everolimus

Sunitinib

Octreotide

Hydroxyurea

Angiogenesis Inhibitors

Growth Inhibitors

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Hormonal

According to local standard practice, treatment in the control arm is left to the investigator's discretion.

* Hydroxyurea
* Bevacizumab
* Sunitinib
* Octreotide (Sandostatin LAR)
* Everolimus
* No treatment (observation with regular follow-up and best supportive care)

Patients will receive 177Lu-DOTATATE with a total dose of 7.4 GBq/cycle every six weeks for four cycles as an IV infusion

According to local standard practice, treatment or no treatment in the control arm is left to the investigator's discretion.

Local standard of Care

177Lu-DOTATATE

EORTC

Nathalie Albert, Prof.

Novel treatments are urgently needed for meningiomas progressing after local therapies (surgery, radiotherapy). So far, no effective systemic therapies are known in this situation. The LUMEN-1 trial will investigate in a prospective randomized trial the efficacy of the precision medicine "theranostic" concept of combining diagnostic patient selection using PET-based molecular imaging and target-specific therapeutic intervention using a systemically administered radioligand.

The rationale for the LUMEN-1 trial is based on the following: (a) high somatostatin receptor (SSTR) expression in meningiomas, (b) wide-spread availability of clinically established SSTR-PET imaging, (c) proven efficacy of SSTR-targeting radioligand therapy using \[177Lu\]Lu-DOTATATE in another tumor type (neuroendocrine tumors), and (d) promising experiences with \[177Lu\]Lu-DOTATATE therapy in compassionate use applications and retrospective case series and interim results from one ongoing uncontrolled prospective trial in meningiomas. LUMEN-1 is the first randomized clinical trial to investigate \[177Lu\]Lu-DOTATATE therapy in refractory meningioma and may open new avenues for treatment and research in this area.

177Lu-DOTATATE for Recurrent Meningioma

177Lu-DOTATATE for Recurrent Meningioma: a Randomized Phase II Study

To examine whether \[177Lu\]Lu-DOTATATE demonstrates sufficient antitumor activity in patients with recurrent meningioma to justify further investigation. Progression-free survival computed based on MRI-based RANO meningioma response criteria as assessed by the local investigator.

Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median OS (mOS)

Best overall response (BOR, defined as CR, MR or PR during study treatment) rate. Complete response (CR) rate is computed by MRI based RANO meningioma response criteria as assessed by the local investigator.

Median best overall response (BOR, defined as CR, MR or PR during study treatment) duration. Median complete response (CR) duration is computed by MRI based RANO meningioma response criteria as assessed by the local investigator.

The magnitude of change in HRQoL in terms of global health status from EORTC QLQ-C30 during treatment.

The magnitude of change in HRQoL in terms of physical functioning from EORTC QLQ-C30 during treatment.

The magnitude of change in HRQoL in terms of motor disfunction from EORTC QLQ-BN20 during treatment.

Change of neurological function (NANO scale) from baseline during study treatment.

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Novartis

European Organisation for Research and Treatment of Cancer - EORTC

Pembrolizumab

Immunomodulating Agents

Participants with recurrent grade II or III meningioma will receive stereotactic radiosurgery. in conjunction with pembrolizumab 200mg IV infusion on day 1 (to -1) of radiation and then every 3 weeks. Participants may be eligible for up to 17 additional cycles of pembrolizumab depending on disease status after completion of first course.

200mg given intravenously (IV) on day 1 (to -1) of radiation and then every 3 weeks until progression or unacceptable toxicity

Given in (a) single session treatment with margin dose of 15-20 Gy to the target for a maximum target volume of 8 cc or (b) five consecutive business days treatment to total dose of 25-30 Gy to the target for a maximum target volume of 20 cc when the target volume exceeds 8 cc or the target is in proximity to critical structures

Neuro-Oncology New Patient Coordinator

Nancy Oberheim Bush, MD, PhD

Steve Braunstein, MD

This phase II trial studies the effect of stereotactic radiosurgery and pembrolizumab in treating patients with meningioma that has come back (recurrent). Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery. Pembrolizumab is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients; an antibody that is made in the lab is also known as a humanized monoclonal antibody. Pembrolizumab is a highly selective humanized monoclonal antibody that is designed to block the action of the receptor PD-1. It has been studied in lab experiments and in other types of cancer. The PD-1 receptor works to keep the immune system from noticing tumor cells. The addition of pembrolizumab to stereotactic radiosurgery may improve the progression free survival of patients with meningioma.

PRIMARY OBJECTIVE:

I. To determine the efficacy of stereotactic radiation and pembrolizumab for treatment of recurrent meningioma compared to historical control based on progression free survival at 12 months (PFS12).

SECONDARY OBJECTIVE:

I. To assess overall survival and further assess progression free survival of stereotactic radiation and pembrolizumab for treatment of recurrent meningioma.

EXPLORATORY OBJECTIVES:

I. To assess immune-related tumor effects pembrolizumab treatment in meningioma using magnetic resonance (MR) imaging in conjunction with assessment by Response Assessment in Neuro-Oncology Criteria (RANO) and Immunotherapy (i)RANO criteria.

II. To assess neurocognitive function and quality of life with pembrolizumab and radiation using the Neurologic Assessment in Neuro-Oncology (NANO) Scale, and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire brain tumour module (QLQ-BN20).

III. To assess safety of the combined treatment modalities in meningioma, through evaluation of grade III adverse events (AEs) and dose-limiting toxicity (DLT).

OUTLINE:

Within -3 to 0 days from the start of stereotactic radiation therapy, patients receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo stereotactic radiosurgery on day 1 or days 1-5 of cycle 1 in the absence of disease progression or unacceptable toxicity.

All participants who have completed the first course, or stopped for complete response, may be eligible for up to an additional 17 cycles of pembrolizumab if there is investigator-determined progressive disease by iRANO after initial treatment.

After completion of study treatment, patients are followed up at 30 days, every 12 weeks for 2 years, and then every 6 months thereafter for up to 5 years.

Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma

A Phase II Study of Stereotactic Radiosurgery in Conjunction With the PD-1 Inhibitor, Pembrolizumab for the Treatment of Recurrent Meningioma

Percentage of patients who are progression-free at the landmark of 12 months from start of treatment based on the target lesion(s) that are receiving radiation treatment will be reported. Tumor progression will be assessed using Immunotherapy Radiologic Assessment in Neuro-oncology Criteria (iRANO) and defined as \> 25% increase in sum of the products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing doses of corticosteroids and/or a significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events.

Overall survival (OS) is defined as the duration of time from start of treatment to time of death estimated from the Kaplan-Meier method.

PFS is defined as the duration of time from start of treatment to time of progression using Immunotherapy Radiologic Assessment in Neuro-oncology Criteria (iRANO) or death estimated from the Kaplan-Meier method, and two-sided 95% confidence intervals (CI) will be computed based on the Greenwood's formula.

Merck Sharp & Dohme LLC

Nancy Ann Oberheim Bush, MD

Principal Investigator

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 of courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Undergo electric field therapy using Optune device

Electric Field Therapy

NovoTTF-200A Device

Quality-of-Life Assessment

Study Coordinator

Santosh Kesari, MD, PhD

Seema Nagpal, MD

Minesh P. Mehta, MD

Erin Dunbar, MD

Priya Kumthekar, MD

Jeffrey Raizer, MD

Karan Dixit, MD

Orin Bloch, MD

James P. Chandler, MD

Sean Grimm, MD

Richard A. Peterson, MD

Arati S. Desai, MD

The purpose of this research study is to determine the effects bevacizumab (the study drug) combined with Optune (the study device) tumor treatment field therapy has on meningiomas. Bevacizumab is considered investigational because the US Food and Drug Administration (FDA) has not approved its use for the treatment of meningiomas. The study drug is a medication that blocks the growth of new blood vessels. It is thought that the study drug may interfere with the growth of new blood vessels and therefore might stop tumor growth, and possibly shrink the tumor by keeping it from receiving nutrients and oxygen supplied by the blood vessels. Optune is also considered investigational because the US FDA has not approved its use for the treatment of meningiomas. Optune is a device that the patient will wear and use for at least 18 hours of each day. It delivers alternating electrical current to the patient's brain tumor and by doing so interrupts a process called mitosis. Mitosis needs to occur in order for cell division to occur and allows tumors to grow. By slowing this process, we hypothesize that meningioma growth may also be slowed.

PRIMARY OBJECTIVES:

I. To determine progression free survival (PFS) for 6 months (PFS-6) in patients with recurrent or progressive meningioma.

SECONDARY OBJECTIVES:

I. To determine overall survival (OS). II. To determine tumor response rate (TRR). III. To assess quality of life with treatment (QOL) using Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes on days 1 and 15 of courses 1-4. Beginning on day 1 of course 5, patients may choose to receive bevacizumab IV every 3 weeks or remain on the every 2-week schedule. Patients also undergo electric field therapy using Optune (formerly NovoTTF-200A System) daily over 18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma

A Phase 2, Single Arm, Multi-center, Open Label Trial Combining Optune With Concurrent Bevacizumab in the Setting of Recurrent or Progressive Meningioma

Determine the efficacy of combination therapy of bevacizumab and Optune (TTF) as assessed by Progression Free Survival at 6 months

OS will be defined from the time of registration to death and will be assessed for up to 2 years.

Imaging (MRI or CT scan) will assess radiographic response in terms of complete response, partial response, stable disease, and progressive disease. The iRANO criteria will be used for response assessment.

To assess QOL with treatment the Functional Assessment of Cancer Therapy-Brain version 4.0 (FACT-Br) questionnaire will be administered.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab and Multi-fraction Stereotactic Radiosurgery With or Without Ipilimumab in Treating Patients With Recurrent Grade II-III Meningioma	NCT03604978	Grade 2 Meningi... Grade 3 Meningi... Recurrent Menin...	Biospecimen Col... Echocardiograph... Ipilimumab Magnetic Resona... Nivolumab Stereotactic Ra...	18 Years -	National Cancer Institute (NCI)
Cabozantinib for Patients With Recurrent or Progressive Meningioma	NCT05425004	Meningioma	Cabozantinib	18 Years -	Baptist Health South Florida
Cabozantinib for Patients With Recurrent or Progressive Meningioma	NCT05425004	Meningioma	Cabozantinib	18 Years -	Baptist Health South Florida
Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy	NCT04082520	Grade 1 Meningi... Grade 2 Meningi... Grade 3 Meningi... Recurrent Menin... Unresectable Me...	Gallium Ga 68-D... Lutetium Lu 177... Magnetic Resona... Positron Emissi... Questionnaire A... Computed Tomogr... Biospecimen Col... Single Photon E...	18 Years -	Mayo Clinic
Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy	NCT04082520	Grade 1 Meningi... Grade 2 Meningi... Grade 3 Meningi... Recurrent Menin... Unresectable Me...	Gallium Ga 68-D... Lutetium Lu 177... Magnetic Resona... Positron Emissi... Questionnaire A... Computed Tomogr... Biospecimen Col... Single Photon E...	18 Years -	Mayo Clinic
177Lu-DOTATATE for Recurrent Meningioma	NCT06326190	Recurrent Menin...	Local standard ... 177Lu-DOTATATE	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma	NCT04659811	Grade I Meningi... Grade II Mening... Grade III Menin... Recurrent Menin...	Pembrolizumab Stereotactic Ra...	18 Years -	University of California, San Francisco
Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma	NCT02847559	Anaplastic (Mal... Atypical Mening... Grade II Mening... Grade III Menin... Recurrent Menin... Supratentorial ...	Bevacizumab Electric Field ... NovoTTF-200A De... Quality-of-Life...	18 Years -	Northwestern University
177Lu-DOTATATE for Recurrent Meningioma	NCT06326190	Recurrent Menin...	Local standard ... 177Lu-DOTATATE	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC

Spots Global Cancer Trial Database for recurrent meningioma