Combination Chemotherapy in Treating Children With Newly Diagnosed Malignant Germ Cell Tumors

Condition(s) targeted: Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor

Intervention: bleomycin sulfate (Biological); filgrastim (Biological); cisplatin (Drug); cyclophosphamide (Drug); etoposide (Drug); conventional surgery (Procedure); MESNA (Biological)

Phase: N/A

Status: Completed

Sponsored by: Children's Oncology Group

Official(s) and/or principal investigator(s):
Marcio A. Malogolowkin, MD, Study Chair, Affiliation: Children's Hospital Los Angeles

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effect on the body of combining cyclophosphamide with cisplatin, etoposide, and bleomycin in treating children who have newly diagnosed malignant germ cell tumors that are not in the brain and gonads.

Official title: Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Feasibility of adding cyclophosphamide to a PEB backbone

Secondary outcome:

Maximum tolerated dose

Estimate the response rate

Detailed description: 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.

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

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

San Jorge Children's Hospital, Santurce 00912, Puerto Rico

Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, Alabama 35294, United States

Phoenix Children's Hospital, Phoenix, Arizona 85016-7710, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Children's & Women's Hospital of British Columbia, Vancouver, British Columbia V6H 3V4, Canada

Southern California Permanente Medical Group, Downey, California 90242-2814, United States

Loma Linda University Cancer Institute at Loma Linda University Medical Center, Loma Linda, California 92354, United States

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

Children's Hospital Central California, Madera, California 93638-8762, United States

Children's Hospital of Orange County, Orange, California 92868, United States

Kaiser Permanente Medical Center - Oakland, Sacramento, California 95825, United States

Children's Hospital and Health Center - San Diego, San Diego, California 92123-4282, United States

Stanford Cancer Center at Stanford University Medical Center, Stanford, California 94305, United States

Children's Hospital Cancer Center, Denver, Colorado 80218-1088, United States

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19899, United States

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States

Lee Cancer Care of Lee Memorial Health System, Fort Myers, Florida 33901, United States

University of Florida Shands Cancer Center, Gainesville, Florida 32610-0232, United States

Nemours Children's Clinic, Jacksonville, Florida 32207, United States

Baptist-South Miami Regional Cancer Program, Miami, Florida 33176, United States

Miami Children's Hospital, Miami, Florida 33155, United States

University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida 33136, United States

Sacred Heart Cancer Center at Sacred Heart Hospital, Pensacola, Florida 32504, United States

All Children's Hospital, St. Petersburg, Florida 33701, United States

St. Joseph's Cancer Institute at St. Joseph's Hospital, Tampa, Florida 33607, United States

Kaplan Cancer Center at St. Mary's Medical Center, West Palm Beach, Florida 33407, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

Cancer Research Center of Hawaii, Honolulu, Hawaii 95813, United States

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States

Saint Jude Midwest Affiliate, Peoria, Illinois 61637, United States

Southern Illinois University School of Medicine, Springfield, Illinois 62794-9620, United States

St. Vincent Indianapolis Hospital, Indianapolis, Indiana 46260, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0293, United States

CancerCare of Maine at Eastern Maine Medial Center, Bangor, Maine 04401, United States

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital, Baltimore, Maryland 21215, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States

C.S. Mott Children's Hospital at University of Michigan, Ann Arbor, Michigan 48109-0238, United States

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States

Hurley Medical Center, Flint, Michigan 48503, United States

Spectrum Health Cancer Care - Butterworth Campus, Grand Rapids, Michigan 49503-2560, United States

Van Elslander Cancer Center at St. John Hospital and Medical Center, Grosse Pointe Woods, Michigan 48236, United States

Breslin Cancer Center at Ingham Regional Medical Center, Lansing, Michigan 48910, United States

Children's Hospital of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States

Fairview University Medical Center - University Campus, Minneapolis, Minnesota 55455, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States

Children's Mercy Hospital, Kansas City, Missouri 64108, United States

Siteman Cancer Center at Barnes-Jewish Hospital, St. Louis, Missouri 63110, United States

Hackensack University Medical Center Cancer Center, Hackensack, New Jersey 07601, United States

St. Barnabas Medical Center, Livingston, New Jersey 07039, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States

SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States

New York Medical College, Valhalla, New York 10595, United States

Janeway Children's Health and Rehabilitation Centre, St. John's, Newfoundland and Labrador A1B 3V6, Canada

Blumenthal Cancer Center at Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States

Presbyterian Cancer Center at Presbyterian Hospital, Charlotte, North Carolina 28233-3549, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

Children's Hospital Medical Center of Akron, Akron, Ohio 44308-1062, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States

Children's Medical Center - Dayton, Dayton, Ohio 45404-1815, United States

Tod Children's Hospital - Forum Health, Youngstown, Ohio 44501, United States

Oklahoma University Medical Center, Oklahoma City, Oklahoma 73104, United States

McMaster Children's Hospital at Hamilton Health Sciences, Hamilton, Ontario L8N 3Z5, Canada

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States

St. Christopher's Hospital for Children, Philadelphia, Pennsylvania 19134-1095, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

Montreal Children's Hospital at McGill University Health Center, Montreal, Quebec H3H 1P3, Canada

Centre Hospitalier Universitaire de Quebec, Ste-Foy, Quebec G1V 4G2, Canada

Allan Blair Cancer Centre at Pasqua Hospital, Regina, Saskatchewan S4T 7T1, Canada

Hollings Cancer Center at Medical University of South Carolina, Charleston, South Carolina 29425, United States

Greenville Hospital System Cancer Center, Greenville, South Carolina 29605, United States

East Tennessee Children's Hospital, Knoxville, Tennessee 37916, United States

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States

Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas 79106, United States

Children's Hospital of Austin, Austin, Texas 78701, United States

Driscoll Children's Hospital, Corpus Christi, Texas 78466, United States

Medical City Dallas Hospital, Dallas, Texas 75230, United States

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104-9958, United States

Baylor University Medical Center - Houston, Houston, Texas 77030-2399, United States

M.D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States

Covenant Children's Hospital, Lubbock, Texas 79410, United States

Methodist Children's Hospital of South Texas, San Antonio, Texas 78229-3993, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, United States

Primary Children's Medical Center, Salt Lake City, Utah 84113-1100, United States

INOVA Fairfax Hospital, Fairfax, Virginia 22031, United States

Carilion Cancer Center of Western Virginia, Roanoke, Virginia 24029, United States

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division, Charleston, West Virginia 25302, United States

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia

St. Vincent Hospital Regional Cancer Center, Green Bay, Wisconsin 54307-3508, United States

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Marshfield Clinic - Marshfield Center, Marshfield, Wisconsin 54449, United States

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2004
Last updated: October 15, 2013