Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors
N/A
21 Years
Both
Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor
Trial Information
Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors
OBJECTIVES:
- Determine the maximum tolerated dose and toxicity profile of cyclophosphamide in
combination with bleomycin, etoposide, and cisplatin in pediatric patients with newly
diagnosed high-risk extracranial, extragonadal malignant germ cell tumors.
- Determine the response rate in patients treated with this regimen.
OUTLINE: This is a pilot, multicenter, dose-escalation study of cyclophosphamide.
- Induction therapy: Patients receive bleomycin IV over 10-20 minutes on day 1, etoposide
IV over 1 hour and cisplatin IV over 4 hours on days 1-5, and cyclophosphamide IV over
1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously once daily
beginning on day 6 and continuing until blood counts recover. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of cyclophosphamide until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity.
Patients are evaluated after 4 courses of therapy. Patients with partial response or stable
disease undergo second-look surgery, receive 2 more courses of induction therapy, and are
then re-evaluated. Patients who do not achieve complete response (CR) after a total of 6
courses may undergo a third surgery. Patients who still have tumor that cannot be removed
are removed from study therapy. Patients who achieve a CR at anytime are followed.
Patients are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3
years.
PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study within 1.3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed extracranial germ cell tumors, including 1
of the following types:
- Yolk sac carcinoma (endodermal sinus tumor)
- Embryonal carcinoma
- Choriocarcinoma
- Teratoma with mixed malignant elements (malignant teratoma)
- High-risk disease, defined as stage III or IV extragonadal germ cell tumors
- Must be enrolled on study within 21 days of diagnostic surgical procedure
PATIENT CHARACTERISTICS:
Age
- 21 and under (at original diagnosis)
Performance status
- ECOG 0-2
- Karnofsky 50-100% (in patients over 16 years of age)
- Lansky 50-100% (in patients 16 years of age and under)
Life expectancy
- At least 2 months
Hematopoietic
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3 (transfusion independent)
- Hemoglobin at least 10.0 g/dL (transfusion allowed)
Hepatic
- Not specified
Renal
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR
- Creatinine based on age as follows:
- No greater than 0.8 mg/dL (5 years and under)
- No greater than 1.0 mg/dL (6-10 years)
- No greater than 1.2 mg/dL (11-15 years)
- No greater than 1.5 mg/dL (over 15 years)
Pulmonary
- FEV_1/FVC greater than 60% OR
- Children who are uncooperative must meet all of the following criteria:
- No dyspnea at rest
- No exercise intolerance
- Pulse oximetry greater than 94%
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy
Surgery
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event Free Survival
Outcome Time Frame:
2 years
Safety Issue:
Yes
Principal Investigator
Marcio A. Malogolowkin, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Children's Hospital Los Angeles
Authority:
United States: Federal Government
Study ID:
AGCT01P1
NCT ID:
NCT00066482
Start Date:
July 2004
Completion Date:
Related Keywords:
- Childhood Germ Cell Tumor
- Extragonadal Germ Cell Tumor
- childhood teratoma
- childhood extragonadal germ cell tumor
- Neoplasms, Germ Cell and Embryonal
Name | Location |
|---|---|
| Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| University of Mississippi Medical Center | Jackson, Mississippi 39216-4505 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Hurley Medical Center | Flint, Michigan 48503 |
| Medical City Dallas Hospital | Dallas, Texas 75230 |
| University of Texas Health Science Center at San Antonio | San Antonio, Texas 78284-7811 |
| Midwest Children's Cancer Center | Milwaukee, Wisconsin 53226 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
| Marshfield Clinic - Marshfield Center | Marshfield, Wisconsin 54449 |
| New York Medical College | Valhalla, New York 10595 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
| University of Miami Sylvester Comprehensive Cancer Center | Miami, Florida 33136 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Cancer Research Center of Hawaii | Honolulu, Hawaii 96813 |
| St. Barnabas Medical Center | Livingston, New Jersey 07039 |
| Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
| Children's Hospital of Orange County | Orange, California 92668 |
| Children's National Medical Center | Washington, District of Columbia 20010-2970 |
| Children's Mercy Hospital | Kansas City, Missouri 64108 |
| Nemours Children's Clinic | Jacksonville, Florida 32207 |
| Miami Children's Hospital | Miami, Florida 33155-4069 |
| All Children's Hospital | St. Petersburg, Florida 33701 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Saint Jude Midwest Affiliate | Peoria, Illinois 61637 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| St. Christopher's Hospital for Children | Philadelphia, Pennsylvania 19134-1095 |
| St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
| Driscoll Children's Hospital | Corpus Christi, Texas 78466 |
| Cook Children's Medical Center - Fort Worth | Fort Worth, Texas 76104 |
| Inova Fairfax Hospital | Falls Church, Virginia 22042-3300 |
| Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
| Southern California Permanente Medical Group | Downey, California 90242 |
| Children's Hospital Central California | Madera, California 93638-8762 |
| Southern Illinois University School of Medicine | Springfield, Illinois 62794-9658 |
| Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
| Children's Medical Center - Dayton | Dayton, Ohio 45404 |
| East Tennessee Children's Hospital | Knoxville, Tennessee 37901 |
| Texas Tech University Health Sciences Center School of Medicine | Amarillo, Texas 79106 |
| Children's Hospital of Austin | Austin, Texas 78701 |
| Covenant Children's Hospital | Lubbock, Texas 79410 |
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock, Arkansas 72205 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Markey Cancer Center at University of Kentucky Chandler Medical Center | Lexington, Kentucky 40536-0084 |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte, North Carolina 28232-2861 |
| Fairview University Medical Center - University Campus | Minneapolis, Minnesota 55455 |
| Oklahoma University Medical Center | Oklahoma City, Oklahoma 73104 |
| M.D. Anderson Cancer Center at University of Texas | Houston, Texas 77030 |
| Stanford Cancer Center at Stanford University Medical Center | Stanford, California 94305 |
| Comprehensive Cancer Center at University of Alabama at Birmingham | Birmingham, Alabama 35294 |
| Loma Linda University Cancer Institute at Loma Linda University Medical Center | Loma Linda, California 92354 |
| Kaiser Permanente Medical Center - Oakland | Sacramento, California 95825 |
| Children's Hospital and Health Center - San Diego | San Diego, California 92123-4282 |
| Lee Cancer Care of Lee Memorial Health System | Fort Myers, Florida 33901 |
| University of Florida Shands Cancer Center | Gainesville, Florida 32610-0232 |
| Baptist-South Miami Regional Cancer Program | Miami, Florida 33176 |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola, Florida 32504 |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa, Florida 33607 |
| Kaplan Cancer Center at St. Mary's Medical Center | West Palm Beach, Florida 33407 |
| St. Vincent Indianapolis Hospital | Indianapolis, Indiana 46260 |
| CancerCare of Maine at Eastern Maine Medial Center | Bangor, Maine 04401 |
| Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore, Maryland 21215 |
| C.S. Mott Children's Hospital at University of Michigan | Ann Arbor, Michigan 48109-0238 |
| Spectrum Health Cancer Care - Butterworth Campus | Grand Rapids, Michigan 49503-2560 |
| Breslin Cancer Center at Ingham Regional Medical Center | Lansing, Michigan 48910 |
| Hackensack University Medical Center Cancer Center | Hackensack, New Jersey 07601 |
| Albert Einstein Cancer Center at Albert Einstein College of Medicine | Bronx, New York 10461 |
| SUNY Upstate Medical University Hospital | Syracuse, New York 13210 |
| Presbyterian Cancer Center at Presbyterian Hospital | Charlotte, North Carolina 28233-3549 |
| Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
| Tod Children's Hospital - Forum Health | Youngstown, Ohio 44501 |
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
| Greenville Hospital System Cancer Center | Greenville, South Carolina 29605 |
| Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas | Dallas, Texas 75390 |
| Baylor University Medical Center - Houston | Houston, Texas 77030-2399 |
| Methodist Children's Hospital of South Texas | San Antonio, Texas 78229-3993 |
| Primary Children's Medical Center | Salt Lake City, Utah 84113-1100 |
| Carilion Cancer Center of Western Virginia | Roanoke, Virginia 24029 |
| West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division | Charleston, West Virginia 25302 |
| St. Vincent Hospital Regional Cancer Center | Green Bay, Wisconsin 54307-3508 |
| James P. Wilmot Cancer Center at University of Rochester Medical Center | Rochester, New York 14642 |
| Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
| Children's Hospital Cancer Center | Denver, Colorado 80218 |
| Children's Hospital of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
