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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00895622
Recruitment Status : Active, not recruiting
First Posted : May 8, 2009
Results First Posted : January 19, 2018
Last Update Posted : January 19, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Radiation: 54 Gy radiotherapy Radiation: 60 Gy radiotherapy Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 244 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Observation for Low-Risk Meningiomas and of Radiotherapy for Intermediate- and High-Risk Meningiomas
Study Start Date : June 2009
Actual Primary Completion Date : September 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Low Risk
No treatment given.
Experimental: Intermediate Risk
54 Gy radiotherapy
Radiation: 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.
Other Names:
  • external beam radiation therapy (EBRT)
  • radiation therapy (RT)
  • Proton therapy
  • Three-dimensional conformal radiotherapy (3D-CRT)
  • Intensity-modulated radiation therapy (IMRT)

Experimental: High Risk
60 Gy radiotherapy
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.
Other Names:
  • external beam radiation therapy (EBRT)
  • radiation therapy
  • Intensity-modulated radiation therapy (IMRT)




Primary Outcome Measures :
  1. Progression-free Survival Rate at 3 Years [ Time Frame: From registration to 3 years ]
    Progression was determined by central review of MRI exams and is defined as an increase in measurable tumor of greater than 20% in any diameter, or as new nodular enhancement in patients with no measurable tumor on initial postoperative imaging. In the absence of neurologic progression (NP), suspected imaging progression of less than 5 mm (maximum diameter) must be confirmed on two successive follow-up MRI studies, a minimum of 3 months apart. NP is defined as a new or progressive neurologic deficit attributed to the meningioma, with or without measurable meningioma growth. Progression-free survival (PFS) rates are estimated using the binomial method.


Secondary Outcome Measures :
  1. Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia] [ Time Frame: From start of radiation to 90 days. ]
    Grades 2-5 neurology, ocular/visual, dermatologic/skin [excluding alopecia] categories, individually and combined for acute adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 where the attribution is related to treatment as definite, probable, possible, or unknown. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

  2. Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia] [ Time Frame: Ninety-one days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 6.3 years. ]
    Grades 2-5 neurology, ocular/visual, dermatologic/skin [excluding alopecia] categories, individually and combined for acute adverse events as assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 where the attribution is related to treatment as definite, probable, possible, or unknown. Late adverse events are those occurring more than 90 days from start of radiation therapy.

  3. Overall Survival Rate at 3 Years [ Time Frame: From registration to 3 years ]
    Overall survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.

  4. Progression-free Survival Rate at 3 Years (Kaplan-Meier Method) [ Time Frame: From registration to 3 years ]
    Progression was determined by central review of MRI exams and is defined as an increase in measurable tumor of greater than 20% in any diameter, or as new nodular enhancement in patients with no measurable tumor on initial postoperative imaging. In the absence of neurologic progression (NP), suspected imaging progression of less than 5 mm (maximum diameter) must be confirmed on two successive follow-up MRI studies, a minimum of 3 months apart. NP is defined as a new or progressive neurologic deficit attributed to the meningioma, with or without measurable meningioma growth. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method.

  5. MRI Imaging Predictors as Assessed by Central Neuroradiology Review at Diagnosis, at Any Failure, and at 3 Years [ Time Frame: From registration to 3 years ]
  6. Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters [ Time Frame: After treatment delivery ]
  7. Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping [ Time Frame: Baseline ]
    A pathology review was conducted both by the institution and centrally, with three possible choices for grade / subtype: World Health Organization (WHO) Grade I / benign; WHO grade II / atypical; WHO grade III / anaplastic. Data is presented for all risk groups combined.

  8. Molecular Correlative Studies [ Time Frame: From registration to 3 years ]
    Biomarker data has not yet been obtained and therefore this outcome measure cannot be reported.

  9. Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis [ Time Frame: From registration to 3 years ]
    Biomarker data has not yet been obtained and therefore this outcome measure cannot be reported.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00895622


  Hide Study Locations
Locations
United States, Arizona
Arizona Oncology Services Foundation
Phoenix, Arizona, United States, 85013
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
United States, Georgia
Emory Crawford Long Hospital
Atlanta, Georgia, United States, 30308
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
United States, Idaho
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Boise, Idaho, United States, 83706
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Indiana
Methodist Cancer Center at Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
Kansas City Cancer Centers - Southwest
Overland Park, Kansas, United States, 66210
CCOP - Kansas City
Prairie Village, Kansas, United States, 66208
United States, Kentucky
Norton Suburban Hospital
Louisville, Kentucky, United States, 40207
United States, Louisiana
Mary Bird Perkins Cancer Center - Baton Rouge
Baton Rouge, Louisiana, United States, 70809
United States, Maine
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, United States, 04074
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
Springfield, Massachusetts, United States, 01107
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
Sparrow Regional Cancer Center
Lansing, Michigan, United States, 48912-1811
St. Joseph Mercy Oakland
Pontiac, Michigan, United States, 48341-2985
Mercy Regional Cancer Center at Mercy Hospital
Port Huron, Michigan, United States, 48060
Seton Cancer Institute at Saint Mary's - Saginaw
Saginaw, Michigan, United States, 48601
St. John Macomb Hospital
Warren, Michigan, United States, 48093
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, United States, 55101
United Hospital
Saint Paul, Minnesota, United States, 55102
United States, Missouri
Kansas City Cancer Centers - South
Kansas City, Missouri, United States, 64131
Kansas City Cancer Centers - North
Kansas City, Missouri, United States, 64154
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Montana
Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Highland Hospital of Rochester
Rochester, New York, United States, 14620
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
United States, Ohio
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
Barberton Citizens Hospital
Barberton, Ohio, United States, 44203
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
Grant Medical Center Cancer Care
Columbus, Ohio, United States, 43215
Lake/University Ireland Cancer Center
Mentor, Ohio, United States, 44060
United States, Oklahoma
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
United States, South Carolina
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0361
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Utah
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, United States, 84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Dixie Regional Medical Center - East Campus
Saint George, Utah, United States, 84770
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Vermont
Norris Cotton Cancer Center - North
Saint Johnsbury, Vermont, United States, 05819
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Washington
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
United States, Wisconsin
St. Mary's Hospital Medical Center - Green Bay
Green Bay, Wisconsin, United States, 54303
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, United States, 54143
Community Memorial Hospital Cancer Care Center
Menomonee Falls, Wisconsin, United States, 53051
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Regional Cancer Center at Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, United States, 53066
Door County Cancer Center at Door County Memorial Hospital
Sturgeon Bay, Wisconsin, United States, 54235-1495
Waukesha Memorial Hospital Regional Cancer Center
Waukesha, Wisconsin, United States, 53188
Canada, Alberta
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1Y 4E9
Canada, Quebec
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: C. Leland Rogers, MD Virginia Commonwealth University

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00895622     History of Changes
Other Study ID Numbers: RTOG-0539
CDR0000641815
First Posted: May 8, 2009    Key Record Dates
Results First Posted: January 19, 2018
Last Update Posted: January 19, 2018
Last Verified: December 2017

Keywords provided by Radiation Therapy Oncology Group:
adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult anaplastic meningioma
adult papillary meningioma
recurrent adult brain tumor

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Meningioma
Neoplasms by Site
Neoplasms
Nervous System Diseases
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms, Vascular Tissue
Meningeal Neoplasms