Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

NCT00053352 | Completed Phase 3 Results DMC

• 5 other identifiers: AGCT0132NCI-2009-00373CDR0000269433COG-AGCT0132U10CA098543
• Study Type: interventional
• Target: 302
• Locations: 6 countries
• Sites: 126

Brief Summary

This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.

Conditions

Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

Outcome Measures

Primary Outcomes (2)

• Event-Free Survival (EFS)

  Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.

  3 Years after enrollment

• Overall Survival (OS)

  Percentage probability of being alive at 3 years following enrollment.

  3 Years after enrollment

Secondary Outcomes (2)

• Days Hospitalized for Patients Who Receive Chemotherapy

  Up to 126 days after the start of chemotherapy

• Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

  Up to 126 days after the start of chemotherapy

Study Arms (2)

Arm I

EXPERIMENTAL

Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes \& etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 \& 6). After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy. After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, \& 16.

Procedure: conventional surgery; Drug: cisplatin; Drug: etoposide; Biological: bleomycin sulfate; Other: laboratory biomarker analysis

Arm 2

NO INTERVENTION

Patients who are enrolled with stage I gonadal tumors receive no further anticancer therapy until evidence of tumor recurrence or the diagnosis of a second malignant neoplasm. Observation only for recurrence or development of an SMN

Interventions

conventional surgery PROCEDURE

Also known as: surgery, conventional

Arm I

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Arm I

etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213

Arm I

bleomycin sulfate BIOLOGICAL

Given IV

Also known as: Blenoxane, BLEO, BLM

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Extracranial germ cell tumor that contains 1 of the following malignant histologies: NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible provided 1 of the 3 histologies listed above is also present in the tumor.
• Yolk sac tumor
• Embryonal carcinoma
• Choriocarcinoma
• Low-risk disease (closed to accrual as of 01/20/10)
• Stage I gonadal tumors (ovarian and testicular)
• Must have undergone complete surgical and radiologic staging to exclude the possibility of \> stage I disease
• Intermediate-risk disease
• Stage II, III, or IV malignant testicular GCT
• Stage II or III malignant ovarian GCT
• Stage I or II malignant extragonadal GCT
• Previously stage I gonadal patients who have relapsed on the low-risk (observation) stratum of this study(closed to accrual as of 01/20/10)
• Patients with immature teratoma or mature teratoma who relapse with a malignant component
• No patients with any of the following diagnoses:
• Stage IV ovarian and stage III-IV extragonadal GCT

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (126)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Miller Children's Hospital

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93636-8762, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609-1809, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868-3874, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Sutter General Hospital

Sacramento, California, 95816, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

University of California San Francisco Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Yale University

New Haven, Connecticut, 06520-8032, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States

Location

Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Memorial Healthcare System - Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, 30322, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31403, United States

Location

University of Hawaii

Honolulu, Hawaii, 96813, United States

Location

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Childrens Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Advocate Hope Children's Hospital

Oak Lawn, Illinois, 60453, United States

Location

Saint Jude Midwest Affiliate

Peoria, Illinois, 61602, United States

Location

Southern Illinois University

Springfield, Illinois, 62702, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University

Detroit, Michigan, 48202, United States

Location

Saint John Hospital and Medical Center

Detroit, Michigan, 48236, United States

Location

Hurley Medical Center

Flint, Michigan, 48502, United States

Location

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Michigan State University - Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Childrens Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Brooklyn Hospital Center

Brooklyn, New York, 11201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

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

New Hyde Park, New York, 11040, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Mission Hospitals Inc

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Medical Center-Fargo

Fargo, North Dakota, 58122, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

The Children's Medical Center of Dayton

Dayton, Ohio, 45404, United States

Location

Mercy Children's Hospital

Toledo, Ohio, 43608, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822-2001, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health Richland

Columbia, South Carolina, 29203, United States

Location

T C Thompson Children's Hospital

Chattanooga, Tennessee, 37403, United States

Location

East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Texas Tech University Health Science Center-Amarillo

Amarillo, Texas, 79106, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

Location

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Childrens Hospital-King's Daughters

Norfolk, Virginia, 23507, United States

Location

Carilion Clinic Children's Hospital

Roanoke, Virginia, 24014, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

West Virginia University Charleston

Charleston, West Virginia, 25304, United States

Location

Saint Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

The Children's Hospital at Westmead

Sydney, New South Wales, 2145, Australia

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6008, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Chedoke-McMaster Hospitals

Hamilton, Ontario, L8S 4L8, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Hospital Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, G1V 4G2, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Starship Children's Hospital

Grafton, Auckland, 1145, New Zealand

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

Swiss Pediatric Oncology Group - Geneva

Geneva, 1205, Switzerland

Location

Related Publications (1)

• O'Neill AF, Xia C, Krailo MD, Shaikh F, Pashankar FD, Billmire DF, Olson TA, Amatruda JF, Villaluna D, Huang L, Malogolowkin M, Rodriguez-Galindo C, Frazier AL. alpha-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium. Cancer. 2019 Oct 15;125(20):3649-3656. doi: 10.1002/cncr.32363. Epub 2019 Jul 29.

  PMID: 31355926 DERIVED

Related Links

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

MeSH Terms

Conditions

Ovarian Germ Cell Cancer; Testicular Neoplasms; Teratoma; Endodermal Sinus Tumor

Interventions

Surgical Procedures, Operative; Congresses as Topic; Cisplatin; Etoposide; Bleomycin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Mesonephroma

Intervention Hierarchy (Ancestors)

Organizations; Health Care Economics and Organizations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Only patients considered eligible contribute to the tabulation of AEs. Arm 1: 182 eligible as described in Participant Flow as 190 enrolled, -8 ineligible. Arm 2: 104 eligible as described in Participant Flow as 112 enrolled, -8 ineligible.

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Anne Frazier, MD

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2003
• First Posted: January 28, 2003
• Study Start: November 3, 2003
• Primary Completion: October 1, 2013
• Study Completion: June 30, 2021
• Last Updated: July 13, 2021
• Results First Posted: December 8, 2017

Record last verified: 2021-07

Locations

PR (1); CA (9); US (112); AU (2); CH (1); NZ (1)