Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

NCT ID: NCT00075582

Last Updated: 2021-11-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-04

Study Completion Date

2021-09-30

Brief Summary

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This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.

Detailed Description

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PRIMARY OBJECTIVES:

I. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and radiotherapy.

SECONDARY OBJECTIVES:

I. Determine local control rates in patients treated with this regimen. II. Determine the rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical group III) and the proportion of second-look surgeries that render patients treated with this regimen tumor-free or with microscopic tumor only and evaluate the pathologic significance of that residual tumor.

III. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.

REGIMEN I (subset 1 patients) \[closed to accrual as of 08/13/2010: Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy\*\*, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.

REGIMEN II (subset 2 patients)\[closed to accrual as of 9/23/2011\]: Patients receive VAC chemotherapy and radiotherapy\*\* as in regimen I and VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin\* IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, and continued VA\* chemotherapy. In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: \*For both regimens, dactinomycin is omitted during radiotherapy.

NOTE: \*\*Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week 13

Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Conditions

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Adult Rhabdomyosarcoma Embryonal Childhood Rhabdomyosarcoma Embryonal-botryoid Childhood Rhabdomyosarcoma Previously Untreated Childhood Rhabdomyosarcoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regimen I (chemotherapy, radiotherapy)

Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)

Group Type EXPERIMENTAL

dactinomycin

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Undergo radiotherapy

Regimen II (chemotherapy, radiotherapy, surgery)

Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).

Group Type EXPERIMENTAL

conventional surgery

Intervention Type PROCEDURE

Some patients may undergo second-look surgery

dactinomycin

Intervention Type DRUG

Given IV

cyclophosphamide

Intervention Type DRUG

Given IV

vincristine sulfate

Intervention Type DRUG

Given IV

radiation therapy

Intervention Type RADIATION

Undergo radiotherapy

Interventions

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conventional surgery

Some patients may undergo second-look surgery

Intervention Type PROCEDURE

dactinomycin

Given IV

Intervention Type DRUG

cyclophosphamide

Given IV

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

radiation therapy

Undergo radiotherapy

Intervention Type RADIATION

Other Intervention Names

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surgery, conventional ACT-D actinomycin C1 AD Cosmegen DACT CPM CTX Cytoxan Endoxan Endoxana leurocristine sulfate VCR Vincasar PFS irradiation radiotherapy therapy, radiation

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:

* Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):

* Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
* Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
* Stage 2 and clinical group I or II disease
* Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):

* Stage 1 and clinical group III disease arising in a non-orbit site
* Stage 3 and clinical group I or II disease
* Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)

* If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
* Prior regional lymph node sampling required for patients with extremity tumors
* None of the following diagnoses:

* Intermediate-risk embryonal RMS
* Metastatic embryonal RMS
* Alveolar RMS
* Undifferentiated sarcoma
* RMS not otherwise specified (NOS)
* Other soft tissue sarcoma, including sarcoma NOS
* Prior enrollment on clinical trial COG-D9902
* Performance status - ECOG 0-2
* Performance status - Karnofsky 50-100% (≥ 16 years old)
* Performance status - Lansky 50-100% (\< 16 years old)
* Absolute neutrophil count at least 750/mm\^3
* Platelet count at least 75,000/mm\^3 (transfusion independent)
* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* Creatinine\* based on age/gender as follows:

* No greater than 0.8 mg/dL for patients age 5 and under
* No greater than 1.0 mg/dL for patients age 6 to 9
* No greater than 1.2 mg/dL for patients age 10 to 12
* No greater than 1.4 mg/dL for female patients age 13 and over
* No greater than 1.5 mg/dL for male patients age 13 to 15
* No greater than 1.7 mg/dL for male patients age 16 and over
* Creatinine clearance\* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m\^2
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled infection
* No prior chemotherapy (except for patients treated on the related intermediate-risk study)
* Prior steroids allowed
* No prior radiotherapy
Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Walterhouse, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

University of Arizona Health Sciences Center

Tucson, Arizona, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Children's Oncology Group

Arcadia, California, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's Hospital

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Site Status

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status

Childrens Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

UC Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Site Status

Memorial Healthcare System - Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Clinic - Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

Baptist Hospital of Miami

Miami, Florida, United States

Site Status

M D Anderson Cancer Center- Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Joseph Children's Hospital of Tampa

Tampa, Florida, United States

Site Status

Saint Mary's Hospital

West Palm Beach, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

University of Hawaii

Honolulu, Hawaii, United States

Site Status

Tripler Army Medical Center

Honolulu, Hawaii, United States

Site Status

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Childrens Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Advocate Hope Children's Hospital

Oak Lawn, Illinois, United States

Site Status

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Site Status

Southern Illinois University

Springfield, Illinois, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

Raymond Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Kosair Children's Hospital

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Children's Hospital-Main Campus

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Maine Children's Cancer Program

Scarborough, Maine, United States

Site Status

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Baystate Medical Center

Springfield, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Michigan State University - Breslin Cancer Center

Lansing, Michigan, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

The Childrens Mercy Hospital

Kansas City, Missouri, United States

Site Status

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Brooklyn Hospital Center

Brooklyn, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Mission Hospitals Inc

Asheville, North Carolina, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Presbyterian Hospital

Charlotte, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

The Children's Medical Center of Dayton

Dayton, Ohio, United States

Site Status

Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Greenville Cancer Treatment Center

Greenville, South Carolina, United States

Site Status

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

University of Vermont

Burlington, Vermont, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Childrens Hospital-King's Daughters

Norfolk, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

West Virginia University Charleston

Charleston, West Virginia, United States

Site Status

Saint Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Sydney Children's Hospital

Randwick, New South Wales, Australia

Site Status

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

Site Status

Sydney West Area Health Service-Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Women's and Children's Hospital-Adelaide

North Adelaide, South Australia, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

Chedoke-McMaster Hospitals

Hamilton, Ontario, Canada

Site Status

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Hospital Sainte-Justine

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Starship Children's Hospital

Grafton, Auckland, New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

San Jorge Children's Hospital

Santurce, , Puerto Rico

Site Status

Swiss Pediatric Oncology Group - Geneva

Geneva, , Switzerland

Site Status

Swiss Pediatric Oncology Group - Lausanne

Lausanne, , Switzerland

Site Status

Countries

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Netherlands United States Australia Canada New Zealand Puerto Rico Switzerland

References

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Woolson RF (1981) Rank-tests and a one-sample log-rank test for comparing observed survival-data to a standard population. Biometrics 37: 687-696.

Reference Type BACKGROUND

Proia AD. Spindle Cell/Sclerosing Rhabdomyosarcoma of the Orbit. Ophthalmic Plast Reconstr Surg. 2023 Jan-Feb 01;39(1):e17-e20. doi: 10.1097/IOP.0000000000002252. Epub 2022 Jul 13.

Reference Type DERIVED
PMID: 35829629 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

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NCI-2009-00425

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-ARST0331

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000347078

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ARST0331

Identifier Type: -

Identifier Source: org_study_id