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

NCT ID: NCT02847559

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-01
• Study Completion Date: 2026-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Anaplastic (Malignant) Meningioma; Atypical Meningioma; Grade II Meningioma; Grade III Meningioma; Recurrent Meningioma; Supratentorial Meningioma

Study Design

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

Study Groups

Treatment (bevacizumab, electric field therapy)

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Electric Field Therapy

Intervention Type: PROCEDURE

Undergo electric field therapy using Optune device

NovoTTF-200A Device

Intervention Type: DEVICE

Undergo electric field therapy using Optune device

Quality-of-Life Assessment

Intervention Type: PROCEDURE

Ancillary studies

Interventions

Bevacizumab

Given IV

Intervention Type: BIOLOGICAL

Electric Field Therapy

Undergo electric field therapy using Optune device

Intervention Type: PROCEDURE

NovoTTF-200A Device

Undergo electric field therapy using Optune device

Intervention Type: DEVICE

Quality-of-Life Assessment

Ancillary studies

Intervention Type: PROCEDURE

Other Intervention Names

Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Avastin; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; NovoTTF-200A; NovoTTF-200A System; NovoTTFields; NovoTumor Treatment Fields; Optune; Optune Device; Quality of Life Assessment

Eligibility Criteria

Inclusion Criteria

• Patients must have a histologic diagnosis of meningioma, World Health Organization (WHO) grade 2 or 3 (atypical or anaplastic)
• Patient's tumor must have a supratentorial component
• Patients must have measurable or non-measurable (evaluable) disease recurrence; recurrence must be documented by magnetic resonance imaging (MRI) or computed tomography (CT) scan
• All patients must have developed recurrent disease/progression (evidence of recurrence to be established by MRI or CT scan with contrast; there is no limit to the number of relapses) after receiving all standard treatments, which must include the following:

• Surgical resection, if possible;
• Definitive radiation therapy for unresectable meningioma, or for recurrent meningioma after resection (Note: At registration, patients must be at least 28 days post-surgery, and must be at least 28 days post-radiation therapy, with resolution of related cytotoxicities down to grade 2)
• Patients may have had previous systemic treatment regimens with the exception of bevacizumab (no limit to number of prior therapies); a 4 week wash-out period prior to registration is mandatory for all systemic treatments
• Life expectancy of at least 12 weeks
• Karnofsky performance status >= 60%
• Patients must have adequate bone marrow, kidney, and liver function, (within 14 days prior to registration), defined as:
• Absolute neutrophil count (ANC) >= 1500/uL (with/without growth factor)
• Hemoglobin (Hgb) >= 9 g/dL (with/without transfusion)
• Platelets >= 100,000/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN)
• Total bilirubin =< 1.5 x institutional ULN
• Serum creatinine =< 1.5 x institutional ULN
• Females of child-bearing potential (FOCBP) and males with partners of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of study treatment; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; likewise, if the female partner of a male patient becomes pregnant or suspect she is pregnant, he should inform his treating physician immediately

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• FOCBP must have a negative serum or urine pregnancy test within 14 days prior to registration on study
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study
• Patients must be able to comply with all protocol requirements

Exclusion Criteria

• Patients who have had major surgery or significant traumatic injury within 4 weeks prior to registration, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that may require major surgery during the course of the study
• Patients who have had minor surgical procedures (with the exception of the placement of porta cath or other central venous access) within 7 days prior to registration
• Patients with infratentorial disease and spinal disease
• Patients may not be receiving any other investigational agents; (i.e. 28-day washout period from prior investigational drug is required)
• Patients may not receive any other anti-cancer therapies, within 28 days prior to registration and throughout the duration of this trial
• Previous treatment with bevacizumab
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab are not eligible
• Patients with active implanted medical device, a skull defect (such as, missing bone with no replacement), a shunt or bullet fragments; examples of active electronic devices include deep brain stimulators, spinal cord stimulators, vagus nerve stimulators, pacemakers, defibrillators, and programmable shunts
• Patients with known sensitivity to conductive hydrogels like the gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes
• Patients with proteinuria within 14 days of registration as demonstrated by either: urine protein creatinine (UPC) ratio >= 1.0 at screening OR urine dipstick for proteinuria 2+ (patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection, and must demonstrate =< 1 g of protein/24 hours to be eligible)
• Patients with a serious non-healing wound, active ulcer, or untreated bone fracture
• Patients with evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• Patients with history of hematemesis or hemoptysis (defined as having bright red blood of 1/2 teaspoon or more per episode) within 28 days prior to registration
• History of myocardial infarction or unstable angina within 6 months of registration
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and /or diastolic blood pressure > 100 mmHg)
• History of stroke or transient ischemic attack within 6 months prior to registration
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• History of abdominal fistula or gastrointestinal perforation within 6 months prior to registration
• Chronic, systemic treatment with immunosuppressive agents; patients who require a stable dose of corticosteroids for control of cerebral edema are eligible; topical or inhaled steroids are also allowed
• Patients who have any severe and/or uncontrolled intercurrent medical conditions including, but not limited to any of the following, are not eligible:

• Ongoing or active wound infection requiring concurrent systemic antibiotic treatment; there is no mandatory duration of time that a patient has to be off antibiotics, but the treating physician has to deem the infection as effectively treated prior to enrollment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia (New York Heart Association [NYHA] criteria)
• Psychiatric illness/social situations that would limit compliance with study requirements, prevent patient comprehension of the nature of, and risk associated with, the study
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Female patients who are pregnant or nursing are not eligible

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NovoCure Ltd.

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Priya Kumthekar, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

John Wayne Cancer Center at Providence St. John's Health Center

Santa Monica, California, United States

Site Status: COMPLETED

Miami Cancer Institute

Miami, Florida, United States

Site Status: COMPLETED

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status: COMPLETED

Northwestern University

Chicago, Illinois, United States

Site Status: RECRUITING

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, United States

Site Status: ACTIVE_NOT_RECRUITING

Northwestern Medicine/ Cadence Health - CDH

Winfield, Illinois, United States

Site Status: RECRUITING

Vidant Medical Center, East Caroling University

Greenville, North Carolina, United States

Site Status: ACTIVE_NOT_RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Study Coordinator

Role: CONTACT

cancertrials@northwestern.edu

(312)695-1301

Facility Contacts

Priya Kumthekar, MD

Role: primary

p-kumthekar@northwestern.edu

312-503-1818

Priya Kumthekar, MD

Role: primary

(630)352-5450

Other Identifiers

STU00203030

Identifier Type: -

Identifier Source: secondary_id

NU 16C02

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2016-01026

Identifier Type: REGISTRY

Identifier Source: secondary_id

NU 16C02

Identifier Type: -

Identifier Source: org_study_id