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

Phase 3

Completed

Conditions: Ovarian Embryonal Carcinoma
Stage IIC Ovarian Germ Cell Tumor
Stage III Malignant Testicular Germ Cell Tumor
Stage IIIA Ovarian Germ Cell Tumor
Childhood Embryonal Tumor
Childhood Extracranial Germ Cell Tumor
Childhood Extragonadal Germ Cell Tumor
Childhood Malignant Testicular Germ Cell Tumor
Childhood Teratoma
Ovarian Yolk Sac Tumor

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

Registration Number: NCT00053352

Lead Sponsor: Children's Oncology Group

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 302

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

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	conventional surgery	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.
Arm I	bleomycin sulfate	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.
Arm I	laboratory biomarker analysis	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.
Arm I	cisplatin	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.
Arm I	etoposide	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.

Primary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS)	3 Years after enrollment	Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
Overall Survival (OS)	3 Years after enrollment	Percentage probability of being alive at 3 years following enrollment.

Secondary Outcome Measures

Name	Time	Method
Days Hospitalized for Patients Who Receive Chemotherapy	Up to 126 days after the start of chemotherapy	Calculated to quantify the treatment cost associated with this regimen.
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	The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy

Trial Locations

Locations (126): West Virginia University Charleston
🇺🇸
Charleston, West Virginia, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Childrens Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Rainbow Babies and Childrens Hospital
🇺🇸
Cleveland, Ohio, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
University of Minnesota Medical Center-Fairview
🇺🇸
Minneapolis, Minnesota, United States
University of Rochester
🇺🇸
Rochester, New York, United States
New York Medical College
🇺🇸
Valhalla, New York, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
Swiss Pediatric Oncology Group - Geneva
🇨🇭
Geneva, Switzerland
Southern Illinois University
🇺🇸
Springfield, Illinois, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Kaiser Permanente-Oakland
🇺🇸
Oakland, California, United States
Childrens Hospital of Orange County
🇺🇸
Orange, California, United States
Miami Children's Hospital
🇺🇸
Miami, Florida, United States
Memorial Healthcare System - Joe DiMaggio Children's Hospital
🇺🇸
Hollywood, Florida, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Miller Children's Hospital
🇺🇸
Long Beach, California, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Saint Jude Midwest Affiliate
🇺🇸
Peoria, Illinois, United States
Broward Health Medical Center
🇺🇸
Fort Lauderdale, Florida, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸
Grand Rapids, Michigan, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸
Boise, Idaho, United States
Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Wayne State University
🇺🇸
Detroit, Michigan, United States
Brooklyn Hospital Center
🇺🇸
Brooklyn, New York, United States
Michigan State University - Breslin Cancer Center
🇺🇸
Lansing, Michigan, United States
Mission Hospitals Inc
🇺🇸
Asheville, North Carolina, United States
New York University Langone Medical Center
🇺🇸
New York, New York, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
🇺🇸
Newark, New Jersey, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Penn State Hershey Children's Hospital
🇺🇸
Hershey, Pennsylvania, United States
Mercy Children's Hospital
🇺🇸
Toledo, Ohio, United States
Palmetto Health Richland
🇺🇸
Columbia, South Carolina, United States
Saint Christopher's Hospital for Children
🇺🇸
Philadelphia, Pennsylvania, United States
East Tennessee Childrens Hospital
🇺🇸
Knoxville, Tennessee, United States
The Children's Medical Center of Dayton
🇺🇸
Dayton, Ohio, United States
Driscoll Children's Hospital
🇺🇸
Corpus Christi, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Childrens Hospital-King's Daughters
🇺🇸
Norfolk, Virginia, United States
Texas Tech University Health Science Center-Amarillo
🇺🇸
Amarillo, Texas, United States
University of Vermont
🇺🇸
Burlington, Vermont, United States
Covenant Children's Hospital
🇺🇸
Lubbock, Texas, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
Scott and White Memorial Hospital
🇺🇸
Temple, Texas, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
British Columbia Children's Hospital
🇨🇦
Vancouver, British Columbia, Canada
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
San Jorge Children's Hospital
🇵🇷
Santurce, Puerto Rico
Chedoke-McMaster Hospitals
🇨🇦
Hamilton, Ontario, Canada
Starship Children's Hospital
🇳🇿
Grafton, Auckland, New Zealand
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Legacy Emanuel Hospital and Health Center
🇺🇸
Portland, Oregon, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Alberta Children's Hospital
🇨🇦
Calgary, Alberta, Canada
Hospital Sainte-Justine
🇨🇦
Montreal, Quebec, Canada
Children's Hospital Colorado
🇺🇸
Aurora, Colorado, United States
Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
🇺🇸
Downey, California, United States
Lee Memorial Health System
🇺🇸
Fort Myers, Florida, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Memorial Health University Medical Center
🇺🇸
Savannah, Georgia, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Advocate Hope Children's Hospital
🇺🇸
Oak Lawn, Illinois, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Cook Children's Medical Center
🇺🇸
Fort Worth, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
Primary Children's Medical Center
🇺🇸
Salt Lake City, Utah, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Carilion Clinic Children's Hospital
🇺🇸
Roanoke, Virginia, United States
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦
Kingston, Ontario, Canada
The Children's Hospital at Westmead
🇦🇺
Sydney, New South Wales, Australia
Centre Hospitalier Universitaire de Quebec
🇨🇦
Ste-Foy, Quebec, Canada
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸
Oakland, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸
Palo Alto, California, United States
Connecticut Children's Medical Center
🇺🇸
Hartford, Connecticut, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Children's Hospital Medical Center of Akron
🇺🇸
Akron, Ohio, United States
Albany Medical Center
🇺🇸
Albany, New York, United States
State University of New York Upstate Medical University
🇺🇸
Syracuse, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸
New Hyde Park, New York, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
St. Jude Children's Research Hospital
🇺🇸
Memphis, Tennessee, United States
T C Thompson Children's Hospital
🇺🇸
Chattanooga, Tennessee, United States
Sanford Medical Center-Fargo
🇺🇸
Fargo, North Dakota, United States
Sutter General Hospital
🇺🇸
Sacramento, California, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Yale University
🇺🇸
New Haven, Connecticut, United States
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Dell Children's Medical Center of Central Texas
🇺🇸
Austin, Texas, United States
University of Alberta Hospital
🇨🇦
Edmonton, Alberta, Canada
University of Hawaii
🇺🇸
Honolulu, Hawaii, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
University of Florida
🇺🇸
Gainesville, Florida, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States

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

Recruitment & Eligibility

Study & Design

Trial Locations

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