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

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.

Study Overview

• Status: Completed
• Conditions: Atypical Meningioma; Grade III Meningioma; Recurrent Meningioma; Anaplastic (Malignant) Meningioma; Grade II Meningioma; Supratentorial Meningioma
• Intervention / Treatment: Biological: Bevacizumab; Procedure: Quality-of-Life Assessment; Procedure: Electric Field Therapy; Device: NovoTTF-200A Device

Detailed Description

PRIMARY OBJECTIVES:

I. TTo determine the efficacy of Optune (TTF) therapy with Bevacizumab as assessed by Progression Free Survival (PFS) at 6 months (PFS-6) in patients with recurrent or progressive meningioma. PFS-6 will be defined from the time of registration to the time of confirmed progression. In cases where this might be unclear, patients may continue on trial and if progression is confirmed later, then the original date where first changes occurred will be used.

SECONDARY OBJECTIVES:

I. To collect the safety and tolerability data of Optune (TTF) therapy in combination with bevacizumab. II. To determine overall survival (OS). III. To determine tumor response rate (TRR). IV. To determine Objective Response Rate (ORR) V. To assess quality of life with treatment (QOL) using FACT-Br questionnaire.

OUTLINE:

This is a trial of Optune with concurrent standard of care treatment bevacizumab. Both treatments can start simultaneously with either starting first, but both must start within a window of 1 week. 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 for at least18 hours. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are responding will remain on study treatment for 6 months.After 6 months, patients may still continue on OPTUNE and Bevacizumab at the discretion of their treating physician. NOTE:At any point, if patients discontinue bevacizumab secondary to side effects, then they may continue Optune alone per treating physician's discretion.

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Center at Providence St. John's Health Center
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Lake Forest, Illinois, United States, 60045
      • Northwestern University- Lake Forest Hospital
    • Winfield, Illinois, United States, 60190
      • Northwestern Medicine/ Cadence Health - CDH
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Vidant Medical Center, East Caroling University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have a histologic diagnosis of meningioma, World Health Organization (WHO) grade 2 or 3 (atypical or anaplastic)
• Patients must have measurable disease recurrence. Recurrence must be documented by MRI scan.
• All patients must have developed recurrent disease/progression (evidence of recurrence to be established by MRI 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 any previous systemic treatment regimens (no limit to number of prior therapies). Patients with prior treatment with bevacizumab are eligible for enrollment into the study, Note: Except for bevacizumab, a 28 day wash-out period prior to registration is mandatory for all systemic treatments
• Patients must be age ≥ 18 years. Both males and females and patients from all ethnic backgrounds are eligible.
• Life expectancy of at least 12 weeks.
• Karnofsky performance status ≥ 60 % (see appendix 1).
• Patients must have adequate bone marrow, kidney, and liver function, (within 14 days prior to registration), defined as: Platelets ≥ 100,000/L, PT/INR/PTT ≤ 1.5x ULN (for patients on warfarin, INR should be maintained within therapeutic limits (either 2-3 or 2.5-3.5 for heart valve patients), AST and 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 spine only 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
• 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

• 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
• Patients with evidence of increased intracranial pressure (midline shift >5mm, clinically significant papilledema, vomiting and nausea, or reduced level of consciousness).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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 15 mg/kg 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.

Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; 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; Procedure: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Electric Field Therapy; Undergo electric field therapy using Optune device; Device: NovoTTF-200A Device; Undergo electric field therapy using Optune device; Other Names: Optune; NovoTTFields; NovoTumor Treatment Fields; Optune Device; NovoTTF-200A; NovoTTF-200A System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival for 6 months (PFS-6)	Determine the efficacy of combination therapy of bevacizumab and Optune (TTF) as assessed by Progression Free Survival at 6 months. PFS-6 will be defined from the time of registration to the time of confirmed progression. In cases where this might be unclear, patients may continue on trial and if progression is confirmed later, then the original date where first changes occurred will be used.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS will be defined from the time of registration to death and will be assessed for up to 2 years.	From time of registration to death, assessed up to 2 years
Quality of Life (QOL) with treatment using FACT-Br questionnaire	To assess QOL with treatment the Functional Assessment of Cancer Therapy-Brain version 4.0 (FACT-Br) questionnaire will be administered.	At baseline, on Day 1 of every cycle, and 1 month after the last dose of study drug
To collect the safety and tolerability data of Optune (TTF) therapy in combination with bevacizumab. To collect the safety and tolerability data of Optune (TTF) therapy in combination with bevacizumab.	To collect the safety and tolerability data for Optune (TTF) in combination with bevacizumab, this endpoint will collect and report the frequency of adverse events by type, severity (grade), timing, and attribution to Optune and bevacizumab, according the NCI-CTCAE version 4.03.	All subjects who receive at least 1 dose of bevacizumab and use the Optune device for at least 1 day will be evaluable for this endpoint. AEs are followed from treatment initiation through 30 days after the last dose.
Tumor Response Rate (TRR)	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. TRR will be assessed in terms of: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).	At baseline and every eight weeks, assessed up to 12 months
To determine Objective Response Rate (ORR)	ORR will be measured via Brain MRI (or CT with contrast if contraindicated). ORR will beassessed in terms of: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).	Imaging studies will be performed at baseline, during week eight (prior to cycle 3), and every eight weeks thereafter (prior to odd number cycles).

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Cancer Institute (NCI); NovoCure Ltd.
• Investigators: Principal Investigator: Priya Kumthekar, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): August 11, 2025
• Study Completion (Actual): May 1, 2026

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimated): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Meningioma; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Bevacizumab; Immunoglobulin G; Disulfides
• Other Study ID Numbers: NU 16C02 (Other Identifier: Northwestern University); P30CA060553 (U.S. NIH Grant/Contract); STU00203030 (CTRP (Clinical Trial Reporting Program)); NCI-2016-01026 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No