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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00895622
Other study ID # RTOG-0539
Secondary ID CDR0000641815
Status Completed
Phase Phase 2
First received
Last updated
Start date June 2009
Est. completion date August 15, 2023

Study information

Verified date August 2023
Source Radiation Therapy Oncology Group
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 244
Est. completion date August 15, 2023
Est. primary completion date September 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
Canada Cross Cancer Institute at University of Alberta Edmonton Alberta
Canada Hopital Notre-Dame du CHUM Montreal Quebec
Canada McGill Cancer Centre at McGill University Montreal Quebec
Canada Ottawa Hospital Regional Cancer Centre - General Campus Ottawa Ontario
United States Summa Center for Cancer Care at Akron City Hospital Akron Ohio
United States Emory Crawford Long Hospital Atlanta Georgia
United States Winship Cancer Institute of Emory University Atlanta Georgia
United States Greenebaum Cancer Center at University of Maryland Medical Center Baltimore Maryland
United States Barberton Citizens Hospital Barberton Ohio
United States Mary Bird Perkins Cancer Center - Baton Rouge Baton Rouge Louisiana
United States Billings Clinic - Downtown Billings Montana
United States Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise Idaho
United States Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx New York
United States Blumenthal Cancer Center at Carolinas Medical Center Charlotte North Carolina
United States Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois
United States Case Comprehensive Cancer Center Cleveland Ohio
United States Cleveland Clinic Taussig Cancer Center Cleveland Ohio
United States Grant Medical Center Cancer Care Columbus Ohio
United States Riverside Methodist Hospital Cancer Care Columbus Ohio
United States Josephine Ford Cancer Center at Henry Ford Hospital Detroit Michigan
United States City of Hope Comprehensive Cancer Center Duarte California
United States University of Florida Shands Cancer Center Gainesville Florida
United States University of Texas Medical Branch Galveston Texas
United States St. Mary's Hospital Medical Center - Green Bay Green Bay Wisconsin
United States St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin
United States Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods Michigan
United States Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania
United States M. D. Anderson Cancer Center at University of Texas Houston Texas
United States Methodist Cancer Center at Methodist Hospital Indianapolis Indiana
United States West Michigan Cancer Center Kalamazoo Michigan
United States Kansas City Cancer Centers - North Kansas City Missouri
United States Kansas City Cancer Centers - South Kansas City Missouri
United States Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City Kansas
United States Sparrow Regional Cancer Center Lansing Michigan
United States Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon New Hampshire
United States Norton Suburban Hospital Louisville Kentucky
United States CCOP - North Shore University Hospital Manhasset New York
United States Bay Area Cancer Care Center at Bay Area Medical Center Marinette Wisconsin
United States Community Memorial Hospital Cancer Care Center Menomonee Falls Wisconsin
United States Lake/University Ireland Cancer Center Mentor Ohio
United States Baptist-South Miami Regional Cancer Program Miami Florida
United States Medical College of Wisconsin Cancer Center Milwaukee Wisconsin
United States Jon and Karen Huntsman Cancer Center at Intermountain Medical Center Murray Utah
United States Yale Cancer Center New Haven Connecticut
United States Long Island Jewish Medical Center New Hyde Park New York
United States Regional Cancer Center at Oconomowoc Memorial Hospital Oconomowoc Wisconsin
United States Val and Ann Browning Cancer Center at McKay-Dee Hospital Center Ogden Utah
United States Oklahoma University Cancer Institute Oklahoma City Oklahoma
United States Methodist Estabrook Cancer Center Omaha Nebraska
United States Nebraska Medical Center Omaha Nebraska
United States Kansas City Cancer Centers - Southwest Overland Park Kansas
United States Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia Pennsylvania
United States Arizona Oncology Services Foundation Phoenix Arizona
United States Mayo Clinic Hospital Phoenix Arizona
United States St. Joseph Mercy Oakland Pontiac Michigan
United States Mercy Regional Cancer Center at Mercy Hospital Port Huron Michigan
United States CCOP - Kansas City Prairie Village Kansas
United States Virginia Commonwealth University Massey Cancer Center Richmond Virginia
United States Highland Hospital of Rochester Rochester New York
United States James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York
United States Mayo Clinic Cancer Center Rochester Minnesota
United States Seton Cancer Institute at Saint Mary's - Saginaw Saginaw Michigan
United States Dixie Regional Medical Center - East Campus Saint George Utah
United States Norris Cotton Cancer Center - North Saint Johnsbury Vermont
United States Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Saint Louis Missouri
United States Regions Hospital Cancer Care Center Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Huntsman Cancer Institute at University of Utah Salt Lake City Utah
United States UCSF Helen Diller Family Comprehensive Cancer Center San Francisco California
United States Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center Savannah Georgia
United States Maine Center for Cancer Medicine and Blood Disorders - Scarborough Scarborough Maine
United States Mayo Clinic Scottsdale Scottsdale Arizona
United States University Cancer Center at University of Washington Medical Center Seattle Washington
United States Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg South Carolina
United States Baystate Regional Cancer Program at D'Amour Center for Cancer Care Springfield Massachusetts
United States Door County Cancer Center at Door County Memorial Hospital Sturgeon Bay Wisconsin
United States St. John Macomb Hospital Warren Michigan
United States Waukesha Memorial Hospital Regional Cancer Center Waukesha Wisconsin

Sponsors (3)

Lead Sponsor Collaborator
Radiation Therapy Oncology Group National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 gradin — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival Rate at 3 Years Progression was determined by central review of magnetic resonance imaging (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. From registration to 3 years
Secondary Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia] 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. From start of radiation to 90 days.
Secondary Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia] 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. Ninety-one days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 6.3 years.
Secondary Overall Survival Rate at 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. From registration to 3 years
Secondary Progression-free Survival Rate at 3 Years (Kaplan-Meier Method) 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. From registration to 3 years
Secondary Number of Participants Determined to Have MRI Imaging Features as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years MRI's were centrally reviewed by the study neuroradiology co-chairs for presence of edema, homogeneous enhancement, calcification, hyperostosis, and brain invasion. Data is presented for all risk groups combined, with time points presented in each column. Neither risk groups nor time points are compared. Baseline, at time of first progression, and at 3 years
Secondary Greatest Single Dimension From MRI as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years MRI's were centrally reviewed by the study neuroradiology co-chairs. Data is presented for all risk groups combined, with time points presented in each column. Neither risk groups nor time points are compared. Baseline, at time of first progression, and at 3 years
Secondary Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters The principle investigator performed a radiotherapy quality assurance (QA) review. After treatment delivery
Secondary Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping 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. Baseline
Secondary Molecular Correlative Studies From registration to 3 years
Secondary Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis From registration to 3 years
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