Neoplasms

Nervous System Diseases

All Conditions

Rare Diseases

Meningioma

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Patients undergo observation after gross total resection.

Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions after gross total resection.

Clinical Observation

Radiation Therapy

C. Leland Rogers, MD

Site Public Contact

Igor J. Barani

Baldassarre Stea

Michael R. Girvigian

Christopher U. Jones

Samantha A. Seaward

Eric L. Chang

Xiao-Tang Kong

Alexis M. Demopoulos

Nicholas A. Blondin

Eric A. Mellon

Michael R. Olson

Sherif Makar

Hsiang-Hsuan M. Yu

Bree R. Eaton

Adam W. Nowlan

Richard Y. Lee

Sean Sachdev

Ken Tatebe

Matthew Koshy

Bruce E. Brockstein

Vinai Gondi

Anupama Chundury

Gary V. Burton

Matthew D. Cheney

John E. Mignano

Eleanor M. Walker

Samir Narayan

Bret E. Friday

Yan Ji

Gregory B. Biedermann

Jiayi Huang

This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.

PRIMARY OBJECTIVES:

I. To determine, in terms of progression-free survival (PFS), the extent of clinical benefit of the addition of adjuvant radiotherapy (RT) to gross total resection (GTR) for patients with newly diagnosed World Health Organization (WHO) grade II meningioma.

SECONDARY OBJECTIVES:

I. Overall survival (OS). II. Disease-specific survival (DSS). III. Toxicity (grade 3+, exclusive of expected alopecia). IV. Neurocognitive function (NCF). V. Outcomes and patient reported outcomes (PRO) measurements. VI. Adherence to protocol-specific target and normal tissue parameters. VII. Concordance measurements of central versus parent-institution pathology. VIII. Tissue microarray construction, and assessment of pHH3 mitotic index and molecular correlates to OS.

OUTLINE: Patients are randomized to 1 of 2 arms after undergoing gross total resection.

ARM I: Patients undergo observation.

ARM II: Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions (59.4 Gy in 33 daily fractions of 1.8 Gy each).

After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months for year 2 and 3, then yearly for 10 years.

Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery

Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Kaplan-Meier method will be used to calculate the PFS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in PFS between the two arms (Peto 1972).

Kaplan-Meier method will be used to calculate the OS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in OS between the two arms (Peto 1972). Cox proportional hazard model will be used to determine the adjusted treatment effect on OS, with patient pretreatment characteristics as covariates.

Will be calculated based on the Kaplan-Meier curve.

Will be calculated using the cumulative incidence function for each arm. The HR for the treatment effect on DSS will be calculated using Gray's method under the competing risk approach, with death due to non-disease related cause treated as the competing risk (Gray 1988). Multivariate analysis on DSS will be performed using the Fine-Gray model, with patient pretreatment characteristics as covariates (Fine 1999).

Will be calculated using the cumulative incidence function for each arm.

Longitudinal analysis will be performed to compare NCF over time between the 2 arms, using the NCF Clinical Trial Battery (CTB) composite score. Early change from baseline in CTB composite score will be evaluated and compared between the 2 arms using 2-sample t tests.

Longitudinal analysis will be performed to compare symptom burden over time between the 2 arms, using the MDASI-BT. Early change from baseline in symptom burden will be evaluated and compared between the 2 arms using 2-sample t tests.

The Kaplan-Meier method will be used to estimate the PFS and OS rates by pHH3 category. The HRs on the effect of pHH3 on PFS and OS, respectively will be calculated using the Cox proportional hazard model and will be tested using the log-rank test. Multivariate analyses will be conducted with patient pretreatment characteristics, such as age and Simpson resection grade, included as covariates.

The number of adverse events will be measured using the CTCAE, version 4

National Cancer Institute (NCI)

NRG Oncology

Symptoms and General Pathology

Recurrence

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

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.

NovoCure Ltd.

Northwestern University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
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

Spots Global Cancer Trial Database for grade ii meningioma