Clinical trial NCT00895622: Observation or Radiation Therapy in Treating Patients With Grade I, Grade II, or Grade III Meningioma
Official title: Phase II Trial of Observation for Low-Risk Meningiomas and of Radiotherapy for Intermediate- and High-Risk Meningiomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult grade I meningioma
adult grade II meningioma
adult grade III meningioma
adult anaplastic meningioma
adult papillary meningioma
recurrent adult brain tumor
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2009-05-08
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Progression-free Survival Rate at 3 Years
timeFrame: From registration to 3 years
Secondary outcomes:
measure: Number of Patients With Grades 2-5 Acute Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
timeFrame: From start of radiation to 90 days.
measure: Number of Patients With Grades 2-5 Late Adverse Events in the Following Categories Individually and Combined: Neurology, Ocular/Visual, Dermatologic/Skin [Excluding Alopecia]
timeFrame: Ninety-one days from start of radiation therapy to last follow-up. Maximum follow-up at time of analysis was 6.3 years.
measure: Overall Survival Rate at 3 Years
timeFrame: From registration to 3 years
measure: Progression-free Survival Rate at 3 Years (Kaplan-Meier Method)
timeFrame: From registration to 3 years
measure: Number of Participants Determined to Have MRI Imaging Features as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years
timeFrame: Baseline, at time of first progression, and at 3 years
measure: Greatest Single Dimension From MRI as Assessed by Central Neuroradiology Review at Diagnosis, at Progression, and at 3 Years
timeFrame: Baseline, at time of first progression, and at 3 years
measure: Adherence to Protocol-specific Target and Normal Tissue Radiotherapy Parameters
timeFrame: After treatment delivery
measure: Concordance Between Central and Parent Institution Histopathologic Grading/Subtyping
timeFrame: Baseline
measure: Molecular Correlative Studies
timeFrame: From registration to 3 years
measure: Histopathologic Correlates of PFS Including Light Microscopy, Immunohistochemical Analysis, and Microarray Analysis
timeFrame: From registration to 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Atlanta
country: United States
facility: Emory Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cancer Centers - Southwest
state: Kansas
city: Prairie Village
country: United States
facility: CCOP - Kansas City
state: Kansas
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center - Baton Rouge
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Regional Cancer Program at D'Amour Center for Cancer Care
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - South
state: Missouri
city: Kansas City
country: United States
facility: Kansas City Cancer Centers - North
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital of Rochester
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center Cancer Care
state: Ohio
city: Mentor
country: United States
facility: Lake/University Ireland Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center - North
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Oconomowoc
country: United States
facility: Regional Cancer Center at Oconomowoc Memorial Hospital
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Door County Cancer Center at Door County Memorial Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Virginia Commonwealth University
name: C. Leland Rogers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.