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

Stage III Malignant Testicular Germ Cell Tumor Clinical Trial

Official title:

A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053352
• Other study ID #: AGCT0132
• Secondary ID: NCI-2009-00373CD
• Status: Completed
• Phase: Phase 3
• Start date: November 3, 2003
• Est. completion date: June 30, 2021

Study information

• Verified date: July 2021
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 302
• Est. completion date: June 30, 2021
• Est. primary completion date: October 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• 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
• Choriocarcinoma
• Germinoma
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Ovarian Embryonal Carcinoma
• Ovarian Neoplasms
• 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
• Teratoma
• Testicular Choriocarcinoma and Yolk Sac Tumor
• Testicular Embryonal Carcinoma
• Testicular Neoplasms

Intervention

Procedure:
• conventional surgery

Drug:
• cisplatin
Given IV
• etoposide
Given IV

Biological:
• bleomycin sulfate
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Overall Survival (OS)	Percentage probability of being alive at 3 years following enrollment.	3 Years after enrollment
Secondary	Days Hospitalized for Patients Who Receive Chemotherapy	Calculated to quantify the treatment cost associated with this regimen.	Up to 126 days after the start of chemotherapy
Secondary	Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0	The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy	Up to 126 days after the start of chemotherapy

External Links

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