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NCT03180268PHASE3Recruiting

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

NRG Oncology

Start Date

9/12/2017

Completion Date

6/15/2027

Summary

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.

Detailed Description

PRIMARY OBJECTIVE: I. To determine 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. 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. Assessment of pHH3 mitotic index and its correlation with progression-free survival (PFS) and OS. IX. Validation of the prognostic value of a 34-gene expression biomarker. X. Validation of the predictive value of a 34-gene expression biomarker in predicting the benefit of radiotherapy. XI. Tissue and specimen collection for future translational research. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo observation. Additionally, patients undergo magnetic resonance imaging (MRI) and blood collection throughout the study. ARM II: Patients undergo intensity-modulated radiation therapy (IMRT) or proton beam radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI and blood collection throughout the study. 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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * PRIOR TO STEP 1 REGISTRATION: * The patient must have a newly diagnosed unifocal intracranial meningioma, gross totally resected, and histologically confirmed as WHO grade II based upon pathology findings at the enrolling institution. WHO grade will be assigned according to WHO 2016 criteria * Gross total resection (GTR) will be interpreted as modified Simpson grade 1-3 without gross residual dural-based or extradural tumor. GTR must be confirmed both by modified Simpson grade and by post-operative magnetic resonance imaging (MRI) findings. The modified Simpson grade can be inferred from the operative report (surgeon does not need to explicitly describe the Simpson grade for the purposes of eligibility) * Step 1 registration must occur within 180 days of the initial surgery; this will provide sufficient time for post-operative imaging confirmation of resection extent after resolution of operative changes. Moreover, it will permit additional surgery if needed to achieve a GTR. Within this 180 day interval, a second surgery is permitted in order to achieve GTR, but even with a second surgery, Step 1 registration must occur within 180 days of the initial resection * GTR must be confirmed on post-operative imaging following the most recent surgery. For protocol enrollment, the assessment of GTR will be made at each site. However, submission of both pre-operative and post-operative MRIs is required for patients. If a second surgery is performed, submission of post-operative MRI is required and pre-operative MRI is required only if obtained. All sequences obtained in the pre- and post-operative MR imaging are to be submitted to National Radiology Group (NRG) Oncology for study registration. The post-operative MRI must be completed within sufficient time to permit step 1 registration within 180 days of the initial resection. These same conditions apply in the setting of a second surgical procedure, although if a second surgery is completed, step 1 registration must still occur with 180 days of initial surgery. Computed tomography (CT) imaging is not required, but may be obtained if desired clinically, for instance to assess calcifications or hyperostosis * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry * NOTE: Central pathology review must occur between steps 1 and 2 of registration. Once appropriate pathology specimens are received, central pathology review will occur within 10 business days, and must confirm WHO grade II meningioma before the patient can proceed to step 2 registration and randomization * PRIOR TO STEP 2 REGISTRATION: * Histologically confirmed diagnosis of WHO grade II meningioma confirmed by central pathology review prior to step 2 registration * Age \>= 18 * History/physical examination, including neurologic examination within 60 days prior to step 2 registration * Post-operative Zubrod performance status 0-1 within 60 days prior to step 2 registration * If the patient is a woman is of childbearing potential, a serum pregnancy test, obtained within 14 days prior to step 2 registration, must be negative, and, if randomized to receive radiation therapy, the woman must agree to use contraception Exclusion Criteria: * Optic nerve sheath meningioma, spinal or other extracranial meningioma, multiple meningiomas, hemangiopericytoma * Definitive evidence of metastatic meningioma (metastasis, although rare, can occur and is exclusionary) * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (carcinoma in situ of the breast, oral cavity, cervix, melanoma in situ, or other non-invasive malignancies are permissible) * Previous radiotherapy to the scalp, cranium, brain, or skull base and radiation-induced meningiomas * Major medical illnesses or psychiatric impairments, which in the investigators opinion, will prevent administration or completion of the protocol therapy and/or preclude informed consent; these include, but are not restricted to: * Unstable angina and/or congestive heart failure requiring hospitalization at the time of step 2 registration * Transmural myocardial infarction within the last 6 months prior to step 2 registration * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of step 2 registration * Type II neurofibromatosis (NF2) * Ailments entailing substantial increases in sensitivity and side effect risk from radiation therapy (ataxia telangiectasia, Nijmegen breakage syndrome, and human immunodeficiency virus (HIV) with CD4 count \< 200 cells/microliter); HIV testing is not required for eligibility for this protocol, and known HIV positive patients are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count \>= 200 cells/microliter within 30 days prior to step 2 registration * Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction). Note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia

Interventions

PROCEDURE

Biospecimen Collection

OTHER

Clinical Observation

RADIATION

Intensity-Modulated Radiation Therapy

OTHER

Laboratory Biomarker Analysis

PROCEDURE

Magnetic Resonance Imaging

RADIATION

Proton Beam Radiation Therapy

OTHER

Quality-of-Life Assessment

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Conditions

Grade 2 MeningiomaIntracranial Meningioma

Locations

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama 35233

United States

Saint Joseph's Hospital and Medical Center

Phoenix, Arizona 85013

United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

Mayo Clinic in Arizona

Scottsdale, Arizona 85259

United States

University of Arizona Cancer Center-Orange Grove Campus

Tucson, Arizona 85704

United States

Banner University Medical Center - Tucson

Tucson, Arizona 85719

United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona 85719

United States

Kaiser Permanente-Anaheim

Anaheim, California 92806

United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California 95603

United States

Kaiser Permanente-Bellflower

Bellflower, California 90706

United States

Kaiser Permanente Dublin

Dublin, California 94568

United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California 90027

United States

Los Angeles General Medical Center

Los Angeles, California 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Memorial Medical Center

Modesto, California 95355

United States

Kaiser Permanente Oakland-Broadway

Oakland, California 94611

United States

Kaiser Permanente-Ontario

Ontario, California 91761

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

Stanford Cancer Institute Palo Alto

Palo Alto, California 94304

United States

Kaiser Permanente-Rancho Cordova Cancer Center

Rancho Cordova, California 95670

United States

Rohnert Park Cancer Center

Rohnert Park, California 94928

United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California 95661

United States

The Permanente Medical Group-Roseville Radiation Oncology

Roseville, California 95678

United States

Sutter Medical Center Sacramento

Sacramento, California 95816

United States

South Sacramento Cancer Center

Sacramento, California 95823

United States

California Pacific Medical Center-Pacific Campus

San Francisco, California 94115

United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California 95051

United States

Kaiser Permanente Cancer Treatment Center

South San Francisco, California 94080

United States

Sutter Solano Medical Center/Cancer Center

Vallejo, California 94589

United States

Hartford Hospital

Hartford, Connecticut 06102

United States

Yale University

New Haven, Connecticut 06520

United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut 06611

United States

Helen F Graham Cancer Center

Newark, Delaware 19713

United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware 19718

United States

Beebe Health Campus

Rehoboth Beach, Delaware 19971

United States

TidalHealth Nanticoke / Allen Cancer Center

Seaford, Delaware 19973

United States

Boca Raton Regional Hospital

Boca Raton, Florida 33486

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida 33442

United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida 33166

United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida 33021

United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida 32207

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida 33136

United States

Miami Cancer Institute

Miami, Florida 33176

United States

AdventHealth Orlando

Orlando, Florida 32803

United States

AdventHealth East Orlando

Orlando, Florida 32822

United States

Memorial Hospital West

Pembroke Pines, Florida 33028

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida 33324

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Grady Health System

Atlanta, Georgia 30303

United States

Emory Proton Therapy Center

Atlanta, Georgia 30308

United States

Piedmont Hospital

Atlanta, Georgia 30309

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

United States

Northside Hospital

Atlanta, Georgia 30342

United States

Northside Hospital-Forsyth

Cumming, Georgia 30041

United States

Piedmont Fayette Hospital

Fayetteville, Georgia 30214

United States

Piedmont Newnan Hospital

Newnan, Georgia 30265

United States

Piedmont Henry Hospital

Stockbridge, Georgia 30281

United States

Queen's Medical Center

Honolulu, Hawaii 96813

United States

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii 96817

United States

Northwestern University

Chicago, Illinois 60611

United States

Rush MD Anderson Cancer Center

Chicago, Illinois 60612

United States

University of Illinois

Chicago, Illinois 60612

United States

Decatur Memorial Hospital

Decatur, Illinois 62526

United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois 60201

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

NorthShore University HealthSystem-Glenbrook Hospital

Glenview, Illinois 60026

United States

NorthShore University HealthSystem-Highland Park Hospital

Highland Park, Illinois 60035

United States

Loyola University Medical Center

Maywood, Illinois 60153

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana 46202

United States

IU Health Methodist Hospital

Indianapolis, Indiana 46202

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa 52242

United States

University of Kansas Cancer Center

Kansas City, Kansas 66160

United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas 66210

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky 40536

United States

The James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky 40202

United States

UofL Health Medical Center Northeast

Louisville, Kentucky 40245

United States

LSU Health Sciences Center at Shreveport

Shreveport, Louisiana 71103

United States

MaineHealth Coastal Cancer Treatment Center

Bath, Maine 04530

United States

MaineHealth Maine Medical Center - Portland

Portland, Maine 04102

United States

MaineHealth Cancer Care Center of York County

Sanford, Maine 04073

United States

MaineHealth Maine Medical Center- Scarborough

Scarborough, Maine 04074

United States

Maryland Proton Treatment Center

Baltimore, Maryland 21201

United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland 21201

United States

Tufts Medical Center

Boston, Massachusetts 02111

United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan 48106

United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan 48109

United States

Chelsea Hospital

Chelsea, Michigan 48118

United States

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan 48038

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Henry Ford Health Saint John Hospital

Detroit, Michigan 48236

United States

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan 49503

United States

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan 48154

United States

MyMichigan Medical Center Saginaw

Saginaw, Michigan 48601

United States

Henry Ford Health Warren Hospital

Warren, Michigan 48093

United States

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan 48322

United States

University of Michigan Health - West

Wyoming, Michigan 49519

United States

Essentia Health Cancer Center

Duluth, Minnesota 55805

United States

Miller-Dwan Hospital

Duluth, Minnesota 55805

United States

Abbott-Northwestern Hospital

Minneapolis, Minnesota 55407

United States

Mayo Clinic in Rochester

Rochester, Minnesota 55905

United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota 55416

United States

Regions Hospital

Saint Paul, Minnesota 55101

United States

University of Mississippi Medical Center

Jackson, Mississippi 39216

United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri 63376

United States

MU Health - University Hospital/Ellis Fischel Cancer Center

Columbia, Missouri 65212

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri 63141

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Siteman Cancer Center-South County

St Louis, Missouri 63129

United States

Billings Clinic Cancer Center

Billings, Montana 59101

United States

Benefis Sletten Cancer Institute

Great Falls, Montana 59405

United States

Logan Health Medical Center

Kalispell, Montana 59901

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey 07920

United States

Englewood Hospital and Medical Center

Englewood, New Jersey 07631

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey 07645

United States

Jersey Shore Medical Center

Neptune City, New Jersey 07753

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey 08903

United States

Rutgers New Jersey Medical School

Newark, New Jersey 07101

United States

Capital Health Medical Center-Hopewell

Pennington, New Jersey 08534

United States

ProCure Proton Therapy Center-Somerset

Somerset, New Jersey 08873

United States

Robert Wood Johnson University Hospital Somerset

Somerville, New Jersey 08876

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico 87106

United States

New York-Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York 11215

United States

Memorial Sloan Kettering Commack

Commack, New York 11725

United States

The New York Hospital Medical Center of Queens

Flushing, New York 11355

United States

Memorial Sloan Kettering Westchester

Harrison, New York 10604

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

NYP/Weill Cornell Medical Center

New York, New York 10065

United States

University of Rochester

Rochester, New York 14642

United States

Memorial Sloan Kettering Nassau

Uniondale, New York 11553

United States

Westchester Medical Center

Valhalla, New York 10595

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina 27599

United States

Case Western Reserve University

Cleveland, Ohio 44106

United States

Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Mercy Cancer Center-Elyria

Elyria, Ohio 44035

United States

Kettering Medical Center

Kettering, Ohio 45429

United States

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio 44060

United States

ProMedica Flower Hospital

Sylvania, Ohio 43560

United States

UHHS-Westlake Medical Center

Westlake, Ohio 44145

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Legacy Mount Hood Medical Center

Gresham, Oregon 97030

United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon 97210

United States

Saint Luke's University Hospital-Bethlehem Campus

Bethlehem, Pennsylvania 18015

United States

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania 19317

United States

Geisinger Medical Center

Danville, Pennsylvania 17822

United States

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania 17837

United States

Lewistown Hospital

Lewistown, Pennsylvania 17044

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania 19111

United States

Temple University Hospital

Philadelphia, Pennsylvania 19140

United States

Geisinger Cancer Services-Pottsville

Pottsville, Pennsylvania 17901

United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania 18711

United States

Lankenau Medical Center

Wynnewood, Pennsylvania 19096

United States

Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina 29316

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Prisma Health Cancer Institute - Faris

Greenville, South Carolina 29605

United States

Prisma Health Cancer Institute - Eastside

Greenville, South Carolina 29615

United States

Prisma Health Cancer Institute - Greer

Greer, South Carolina 29650

United States

Prisma Health Cancer Institute - Seneca

Seneca, South Carolina 29672

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas 75390

United States

UT MD Anderson Cancer Center

Houston, Texas 77030

United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas 78229

United States

American Fork Hospital / Huntsman Intermountain Cancer Center

American Fork, Utah 84003

United States

Logan Regional Hospital

Logan, Utah 84321

United States

Intermountain Medical Center

Murray, Utah 84107

United States

McKay-Dee Hospital Center

Ogden, Utah 84403

United States

Utah Valley Regional Medical Center

Provo, Utah 84604

United States

Riverton Hospital

Riverton, Utah 84065

United States

LDS Hospital

Salt Lake City, Utah 84143

United States

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont 05819

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

University of Washington Medical Center - Montlake

Seattle, Washington 98195

United States

Legacy Salmon Creek Hospital

Vancouver, Washington 98686

United States

Langlade Hospital and Cancer Center

Antigo, Wisconsin 54409

United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin 54701

United States

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin 53718

United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin 53792

United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin 54449

United States

Froedtert Menomonee Falls Hospital

Menomonee Falls, Wisconsin 53051

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53226

United States

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin 54548

United States

Drexel Town Square Health Center

Oak Creek, Wisconsin 53154

United States

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin 54868

United States

Aspirus Cancer Care - Stevens Point

Stevens Point, Wisconsin 54481

United States

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin 54482

United States

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin 53188

United States

Aspirus Regional Cancer Center

Wausau, Wisconsin 54401

United States

Marshfield Medical Center - Weston

Weston, Wisconsin 54476

United States

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin 54494

United States

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta T2N 5G2

Canada

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario L8V 5C2

Canada

London Regional Cancer Program

London, Ontario N6A 4L6

Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario M5G 2M9

Canada

CHUM - Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec H2X 3E4

Canada

The Research Institute of the McGill University Health Centre (MUHC)

Montreal, Quebec H3H 2R9

Canada

Allan Blair Cancer Centre

Regina, Saskatchewan S4T 7T1

Canada

Tata Memorial Hospital

Mumbai, 400 012

India

Hokkaido University Hospital

Sapporo, Hokkaido 060-8648

Japan

Iwate Medical University Hospital

Shiwa-gun, Iwate 028-3695

Japan

Kyorin University Hospital

Mitaka-shi, Tokyo 181-8611

Japan

Keio University

Shinjuku-ku, Tokyo 160-8582

Japan

Hiroshima University Hospital

Hiroshima, 734-8551

Japan

Saitama Medical University International Medical Center

Saitama, 350-1298

Japan

National Cancer Center Hospital

Tokyo, 104 0045

Japan

King Faisal Specialist Hospital and Research Centre

Riyadh, 11211

Saudi Arabia