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

NCT ID: NCT00053352

Last Updated: 2021-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-03
• Study Completion Date: 2021-06-30

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.

Detailed Description

OBJECTIVES:

I. Determine whether children with newly diagnosed low- or intermediate-risk extracranial germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin, etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10).

II. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.

III. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.

IV. Determine the acute toxic effects of compressed therapy in these patients. V. Determine the long-term sequelae in patients treated with this regimen. VI. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.

VII. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study.

VIII. Determine the cytogenetic and molecular genetic features in patients treated with this regimen.

OUTLINE: Patients are stratified according to disease risk (low vs intermediate).

SURGERY: Patients undergo surgical resection.

Low-risk disease: Patients with gonadal primaries and no evidence of disease after surgery undergo monitoring for disease progression. Patients who remain disease free receive no further treatment. Patients who have disease progression after surgery receive compressed induction chemotherapy. (closed to accrual as of 01/20/2010)

Intermediate-risk disease: After surgery, patients proceed to compressed induction chemotherapy.

COMPRESSED INDUCTION CHEMOTHERAPY: Patients receive cisplatin IV over 90 minutes and etoposide IV over 90 minutes on days 1-3 and bleomycin IV over ≥ 10 minutes on day 1. Treatment repeats every 3 weeks for 3 courses (weeks 0, 3, and 6).

After completion of compressed induction chemotherapy, patients who have 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 who have abnormal tumor markers proceed to second-look surgery and/or 3 more courses of compressed consolidation chemotherapy.

SECOND-LOOK SURGERY: Patients undergo surgical resection of residual tumor. After surgery, patients who are in 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.

COMPRESSED CONSOLIDATION CHEMOTHERAPY: Patients receive cisplatin, etoposide, and bleomycin as in induction chemotherapy in weeks 10, 13, and 16.

Patients are followed up monthly for 6 months, every 3 months for 18 months, and then annually for up to 10 years.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

conventional surgery

Intervention Type: PROCEDURE

cisplatin

Intervention Type: DRUG

Given IV

etoposide

Intervention Type: DRUG

Given IV

bleomycin sulfate

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm 2

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

conventional surgery

Intervention Type: PROCEDURE

cisplatin

Given IV

Intervention Type: DRUG

etoposide

Given IV

Intervention Type: DRUG

bleomycin sulfate

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

surgery, conventional; CACP; CDDP; CPDD; DDP; EPEG; VP-16; VP-16-213; Blenoxane; BLEO; BLM

Eligibility Criteria

Inclusion Criteria

• 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
• Intracranial GCT
• Pure mature or immature teratoma, pure dysgerminoma, or seminoma
• Patients with a non-germ cell component in their GCT (e.g., primitive neuroectodermal tumors or rhabdomyosarcoma)
• Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known

• If > 5 days have elapsed from the time of obtaining original markers, tumor markers must be repeated before enrollment of low-risk patients and before initiating therapy in intermediate-risk patients (the results of the repeated tumor markers do not have to be known at the time of study enrollment)
• Must be enrolled within 6 weeks of original diagnostic surgery
• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:

• ≤ 0.4 mg/dL (for patients 1 to 5 months of age)
• ≤ 0.5 mg/dL (for patients 6 to 11 months of age)
• ≤ 0.6 mg/dL (for patients 1 year of age)
• ≤ 0.8 mg/dL (for patients 2 to 5 years of age)
• ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
• ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
• ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
• ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
• ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)
• No prior chemotherapy
• No prior radiotherapy

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Frazier, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Southern California Permanente Medical Group

Downey, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Miller Children's Hospital

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital Central California

Madera, California, United States

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Childrens Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Sutter General Hospital

Sacramento, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

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

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Lee Memorial Health System

Fort Myers, Florida, United States

University of Florida

Gainesville, Florida, United States

Memorial Healthcare System - Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Miami Children's Hospital

Miami, Florida, United States

All Children's Hospital

St. Petersburg, Florida, United States

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

University of Hawaii

Honolulu, Hawaii, United States

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Childrens Memorial Hospital

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Advocate Hope Children's Hospital

Oak Lawn, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Southern Illinois University

Springfield, Illinois, United States

University of Kentucky

Lexington, Kentucky, United States

Kosair Children's Hospital

Louisville, Kentucky, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Wayne State University

Detroit, Michigan, United States

Saint John Hospital and Medical Center

Detroit, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Michigan State University - Breslin Cancer Center

Lansing, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

The Childrens Mercy Hospital

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Saint Peter's University Hospital

New Brunswick, New Jersey, United States

UMDNJ - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Brooklyn Hospital Center

Brooklyn, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

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

New Hyde Park, New York, United States

New York University Langone Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

New York Medical College

Valhalla, New York, United States

Mission Hospitals Inc

Asheville, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Sanford Medical Center-Fargo

Fargo, North Dakota, United States

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

The Children's Medical Center of Dayton

Dayton, Ohio, United States

Mercy Children's Hospital

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Palmetto Health Richland

Columbia, South Carolina, United States

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Texas Tech University Health Science Center-Amarillo

Amarillo, Texas, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Driscoll Children's Hospital

Corpus Christi, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Covenant Children's Hospital

Lubbock, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Scott and White Memorial Hospital

Temple, Texas, United States

Primary Children's Medical Center

Salt Lake City, Utah, United States

University of Vermont

Burlington, Vermont, United States

Childrens Hospital-King's Daughters

Norfolk, Virginia, United States

Carilion Clinic Children's Hospital

Roanoke, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

West Virginia University Charleston

Charleston, West Virginia, United States

Saint Vincent Hospital

Green Bay, Wisconsin, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Alberta Children's Hospital

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Chedoke-McMaster Hospitals

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Hospital Sainte-Justine

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Starship Children's Hospital

Grafton, Auckland, New Zealand

San Jorge Children's Hospital

Santurce, , Puerto Rico

Swiss Pediatric Oncology Group - Geneva

Geneva, , Switzerland

Countries

United States; Australia; Canada; New Zealand; Puerto Rico; Switzerland

References

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.

Reference Type: DERIVED

PMID: 31355926 (View on PubMed)

Related Links

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

NCI-2009-00373

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000269433

Identifier Type: OTHER

Identifier Source: secondary_id

COG-AGCT0132

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AGCT0132

Identifier Type: -

Identifier Source: org_study_id