Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma

NCT ID: NCT00895622

Last Updated: 2023-09-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-06-30

Study Completion Date

2023-08-15

Brief Summary

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RATIONALE: Sometimes a tumor may not need treatment until it progresses. In this case, observation may be sufficient. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor, such as 3-dimensional conformal radiation therapy and intensity-modulated radiation therapy, may kill more tumor cells and cause less damage to normal tissue. It is not yet known whether observation is more effective than radiation therapy in treating patients with meningioma.

PURPOSE: This phase II trial is studying observation to see how well it works compared with radiation therapy in treating patients with grade I, grade II, or grade III meningioma.

Detailed Description

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OBJECTIVES:

Primary

* To estimate the rates of progression-free survival at 3 years in patients with low-risk meningioma undergoing observation and in patients with intermediate- or high-risk meningioma undergoing radiotherapy.

Secondary

* To study the concordance, or lack thereof, between central and parent institution histopathologic diagnosis, grading, and subtyping.
* To estimate the rates of overall survival at 3 years in these patients.
* To estimate the incidence rates of acute and late adverse events ≥ grade 2 in patients with intermediate- or high-risk meningioma undergoing radiotherapy.
* To evaluate MRI imaging predictors by central neuroradiology review at diagnosis, at any failure, and at 3 years.
* To evaluate adherence to protocol-specific target and normal tissue radiotherapy parameters.

This is a multicenter study. Patients are assigned to 1 of 3 groups according to risk.

After completion of study treatment, patients are followed up every 3-6 months for 3 years and then annually for 10 years.

Conditions

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Brain and Central Nervous System Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Low Risk

No treatment given.

Group Type NO_INTERVENTION

No interventions assigned to this group

Intermediate Risk

54 Gy radiotherapy

Group Type EXPERIMENTAL

54 Gy radiotherapy

Intervention Type RADIATION

External beam radiation therapy (EBRT) to a total dose of 54 Gy (RBE) in 30 fractions. 1.8 Gy (RBE) daily, 5 fractions per week, excluding weekends. 3D-CRT or IMRT or Proton allowed.

High Risk

60 Gy radiotherapy

Group Type EXPERIMENTAL

60 Gy radiotherapy

Intervention Type RADIATION

External beam radiation therapy using intensity-modulated radiation therapy (IMRT) to a total dose of 60 Gy in 30 fractions. 2.0 Gy daily, 5 fractions per week, excluding weekends.

Interventions

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54 Gy radiotherapy

External beam radiation therapy (EBRT) to a total dose of 54 Gy (RBE) in 30 fractions. 1.8 Gy (RBE) daily, 5 fractions per week, excluding weekends. 3D-CRT or IMRT or Proton allowed.

Intervention Type RADIATION

60 Gy radiotherapy

External beam radiation therapy using intensity-modulated radiation therapy (IMRT) to a total dose of 60 Gy in 30 fractions. 2.0 Gy daily, 5 fractions per week, excluding weekends.

Intervention Type RADIATION

Other Intervention Names

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external beam radiation therapy (EBRT) radiation therapy (RT) Proton therapy Three-dimensional conformal radiotherapy (3D-CRT) Intensity-modulated radiation therapy (IMRT) external beam radiation therapy (EBRT) radiation therapy Intensity-modulated radiation therapy (IMRT)

Eligibility Criteria

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Inclusion Criteria

1. A histologically documented World Health Organization (WHO) grade I, II, or III meningioma, newly diagnosed or recurrent, and of any resection extent, confirmed by central pathology review. Patients are partitioned according to three groupings: Group I (low risk), Group II (intermediate risk), and Group III (high risk) as defined below:

* Group I (low risk): Patients with a newly diagnosed WHO grade I meningioma that has been gross totally resected (Simpson's grade I, II, or III resections, with no residual nodular enhancement on postoperative imaging) or subtotally resected (residual nodular enhancement or Simpson grade IV or V excision). The extent of resection will be based upon the neurosurgeons' assessment and postoperative MR imaging.
* Group II (intermediate risk): Patients with a newly diagnosed gross totally resected WHO grade II meningioma or patients with a recurrent WHO grade I meningioma irrespective of the resection extent. Resection extent will be recorded on the same basis described above for the low-risk group.
* Group III (high risk): Patients with a newly diagnosed or a recurrent WHO grade III meningioma of any resection extent; patients with a recurrent WHO grade II meningioma of any resection extent; or patients with a newly diagnosed subtotally resected WHO grade II meningioma. In the setting of a newly diagnosed meningioma, the histologic diagnosis must have been reached within 6 months of Step 2 registration. Resection extent will be recorded on the same basis described above for the low-risk group.
* 1.1 In the setting of a newly diagnosed meningioma, the histologic diagnosis must have been reached within 24 weeks prior to Step 2 registration. In the setting of a recurrent meningioma, there are no such time constraints. Additional resection or biopsy is encouraged for patients with recurrence but is not requisite. If further biopsy or resection is performed at recurrence, these specimens must be submitted; submission of the original pathology specimens is encouraged but not required. The diagnosis of recurrence solely on the basis of imaging findings is permitted, but if no additional resection is performed, specimens from prior resection must be submitted.
* 1.2 In cases of newly diagnosed or surgically treated recurrent meningioma, the operating neurosurgeon must provide a Simpson grade for the degree of resection.
2. History/physical examination, including neurologic examination, within 8 weeks prior to Step 2 registration
3. Zubrod Performance Status 0-1
4. Age ≥ 18
5. All patients must have a magnetic resonance imaging (MRI) scan within 12 weeks prior to Step 2 registration. Both preoperative and postoperative MRIs are required for all newly diagnosed patients in groups I, II, or III. In the setting of group II or III patients with recurrent/progressive meningioma and without recent surgery, a pre-operative study may not apply, although MRI documentation of recurrence or progression is required. MRIs must include precontrast T1, T2, and flair images and multiplanar (axial, sagittal, and coronal) postcontrast T1. The postoperative study must be completed within 12 weeks of surgery.

* 5.1 Group I: All group I patients will have surgery. Preoperative and postoperative MRIs are thus required in order to assess resection extent.
* 5.2 Group II: Surgery will be undertaken for the subgroup with a gross totally resected WHO grade II meningioma. For these patients preoperative and postoperative MRIs are necessitated. For the other subgroup with recurrent WHO grade I meningioma, preoperative and postoperative MRIs are required if surgery is undertaken for the recurrent/progressive tumor. However, only the follow-up imaging documenting recurrence or progression will apply if further surgery is not completed.
* 5.3 Group III: Surgery will be undertaken for the subgroup with a newly diagnosed WHO grade III meningioma. For these patients preoperative and postoperative MRIs are obligatory. For the subgroups with recurrent WHO grade II or III meningioma, preoperative and postoperative MRIs are required if surgery is undertaken for the recurrent/progressive tumor. However, only the follow-up imaging documenting recurrence or progression will apply if further surgery is not completed.
6. For woman of childbearing potential who are intermediate or high risk:

* 6.1 Negative serum pregnancy test within 14 days prior to Step 2 registration
* 6.2 The patient must agree to practice adequate contraception from the time of the negative serum pregnancy test throughout the entire course of EBRT.
7. Patient must sign study-specific informed consent prior to study entry

Exclusion Criteria

1. Extracranial meningioma
2. Multiple meningiomas
3. Hemangiopericytoma
4. Major medical illnesses or psychiatric impairments which, in the investigators opinion, will prevent administration or completion of the protocol therapy or preclude informed consent
5. Previous radiation therapy to the scalp, cranium, brain, or skull base
6. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
7. Patients with severe, active comorbidity including, but not restricted to:

* 7.1 Unstable angina and/or congestive heart failure requiring hospitalization at the time of Step 2 registration
* 7.2 Transmural myocardial infarction within the last 6 months
* 7.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of Step 2 registration
* 7.4 Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of Step 2 registration
* 7.5 Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects. Note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.
* 7.6 Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
* 7.7 Active connective tissue disorders such as lupus or scleroderma if the patient is intermediate or high risk
8. Inability to receive gadolinium
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

NRG Oncology

OTHER

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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C. Leland Rogers, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

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Arizona Oncology Services Foundation

Phoenix, Arizona, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Baptist-South Miami Regional Cancer Program

Miami, Florida, United States

Site Status

Emory Crawford Long Hospital

Atlanta, Georgia, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Kansas City Cancer Centers - Southwest

Overland Park, Kansas, United States

Site Status

CCOP - Kansas City

Prairie Village, Kansas, United States

Site Status

Norton Suburban Hospital

Louisville, Kentucky, United States

Site Status

Mary Bird Perkins Cancer Center - Baton Rouge

Baton Rouge, Louisiana, United States

Site Status

Maine Center for Cancer Medicine and Blood Disorders - Scarborough

Scarborough, Maine, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Baystate Regional Cancer Program at D'Amour Center for Cancer Care

Springfield, Massachusetts, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Sparrow Regional Cancer Center

Lansing, Michigan, United States

Site Status

St. Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Mercy Regional Cancer Center at Mercy Hospital

Port Huron, Michigan, United States

Site Status

Seton Cancer Institute at Saint Mary's - Saginaw

Saginaw, Michigan, United States

Site Status

St. John Macomb Hospital

Warren, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

Kansas City Cancer Centers - South

Kansas City, Missouri, United States

Site Status

Kansas City Cancer Centers - North

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Billings Clinic - Downtown

Billings, Montana, United States

Site Status

Methodist Estabrook Cancer Center

Omaha, Nebraska, United States

Site Status

Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

Highland Hospital of Rochester

Rochester, New York, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Site Status

Barberton Citizens Hospital

Barberton, Ohio, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States

Site Status

Grant Medical Center Cancer Care

Columbus, Ohio, United States

Site Status

Lake/University Ireland Cancer Center

Mentor, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Site Status

University of Texas Medical Branch

Galveston, Texas, United States

Site Status

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Site Status

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

Ogden, Utah, United States

Site Status

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Site Status

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

Site Status

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, United States

Site Status

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

Site Status

St. Mary's Hospital Medical Center - Green Bay

Green Bay, Wisconsin, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States

Site Status

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, United States

Site Status

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Regional Cancer Center at Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Site Status

Door County Cancer Center at Door County Memorial Hospital

Sturgeon Bay, Wisconsin, United States

Site Status

Waukesha Memorial Hospital Regional Cancer Center

Waukesha, Wisconsin, United States

Site Status

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, Canada

Site Status

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Site Status

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

Site Status

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Rogers CL, Perry A, Pugh S, Vogelbaum MA, Brachman D, McMillan W, Jenrette J, Barani I, Shrieve D, Sloan A, Bovi J, Kwok Y, Burri SH, Chao ST, Spalding AC, Anscher MS, Bloom B, Mehta M. Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539. Neuro Oncol. 2016 Apr;18(4):565-74. doi: 10.1093/neuonc/nov247. Epub 2015 Oct 22.

Reference Type RESULT
PMID: 26493095 (View on PubMed)

Rogers CL, Won M, Vogelbaum MA, Perry A, Ashby LS, Modi JM, Alleman AM, Galvin J, Fogh SE, Youssef E, Deb N, Kwok Y, Robinson CG, Shu HK, Fisher BJ, Panet-Raymond V, McMillan WG, de Groot JF, Zhang P, Mehta MP. High-risk Meningioma: Initial Outcomes From NRG Oncology/RTOG 0539. Int J Radiat Oncol Biol Phys. 2020 Mar 15;106(4):790-799. doi: 10.1016/j.ijrobp.2019.11.028. Epub 2019 Nov 29.

Reference Type DERIVED
PMID: 31786276 (View on PubMed)

Rogers L, Zhang P, Vogelbaum MA, Perry A, Ashby LS, Modi JM, Alleman AM, Galvin J, Brachman D, Jenrette JM, De Groot J, Bovi JA, Werner-Wasik M, Knisely JPS, Mehta MP. Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539. J Neurosurg. 2018 Jul;129(1):35-47. doi: 10.3171/2016.11.JNS161170. Epub 2017 Oct 6.

Reference Type DERIVED
PMID: 28984517 (View on PubMed)

Other Identifiers

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CDR0000641815

Identifier Type: -

Identifier Source: secondary_id

RTOG-0539

Identifier Type: -

Identifier Source: org_study_id

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