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

NCT00066482 | Completed DMC

• 2 other identifiers: AGCT01P1CDR0000316244
• Study Type: interventional
• Target: 19
• Locations: 4 countries
• Sites: 98

Brief Summary

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.

Conditions

Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor

Keywords

childhood teratoma; childhood extragonadal germ cell tumor

Outcome Measures

Primary Outcomes (1)

• Feasibility of adding cyclophosphamide to a PEB backbone

  2 years

Secondary Outcomes (2)

• Maximum tolerated dose

  21 days

• Estimate the response rate

  Length of study

Study Arms (1)

combination chemotherapy

EXPERIMENTAL

Induction therapy: bleomycin sulfate 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. MESNA \& 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. 6 patients receive escalating doses of cyclophosphamide until the maximum tolerated dose (MTD) is determined. Evaluated after 4 courses of therapy. Partial response or stable disease undergo second-look conventional surgery \& receive 2 more courses of induction therapy then re-evaluated. Those who do not achieve complete response (CR) after a total of 6 courses may undergo a third conventional surgery. Tumor that cannot be removed are removed from study therapy. Achievement of a CR at anytime are followed monthly for 1 year, every 6 months for 1 year, and then annually for 3 years.

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

Interventions

bleomycin sulfate BIOLOGICAL

Given IV over 10 minutes. Children ≥ 12 months: 15 units/m2/dose Children \< 12 months: 0.5 units/kg/dose Day 1 (Week 1, 4, 7, 10)

Also known as: BLEO, BLM, Blenoxane, NSC #125066

combination chemotherapy

filgrastim BIOLOGICAL

Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC \> 5,000/uL

Also known as: GRANULOCYTE COLONY-STIMULATING FACTOR, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629

combination chemotherapy

cisplatin DRUG

Children ≥ 12 months: Given IV over one hour Dose: 20 mg/m2/dose Days 1-5 (Week 1,4,7,10) Children \< 12 months: Given IV over 4 hours, 0.67 mg/kg/dose Days 1-5 (Week 1,4,7,10)

Also known as: Cis-diamminedichloroplatinum II, Platinol-AQ, NSC #119875

combination chemotherapy

cyclophosphamide DRUG

Given IV over 1 hour. Children ≥ 12 months: Level 1: 1.2 g/m2/dose Level 2: 1.8 g/m2/dose Level 3: 2.4 g/m2/dose Children \< 12 months: Level 1: 40 mg/kg/dose Level 2: 60 mg/kg/dose Level 3: 80 mg/kg/dose Day 1 (Week 1, 4, 7, 10)

Also known as: Cytoxan, NSC #026271

combination chemotherapy

etoposide DRUG

Given IV over 1 hour. Children ≥ 12 months: 100 mg/m2/dose Children \< 12 months: 3.3 mg/kg/dose Day 1-5 (Week 1, 4, 7, 10)

Also known as: VP-16, VePesid, Etopophos, NSC #141540

combination chemotherapy

conventional surgery PROCEDURE

Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy

combination chemotherapy

MESNA BIOLOGICAL

Given IV or oral. The total daily MESNA dose is equal to at least 80% of the daily CPM dose. The oral dose of MESNA is 2x the IV dose. Day 1 (Week 1,4,7,10) To be given with CPM.

Also known as: sodium 2-mercaptoethane sulfonate, Mesnex, NSC #113891

combination chemotherapy

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (98)

Comprehensive Cancer Center at University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242-2814, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93638-8762, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Kaiser Permanente Medical Center - Oakland

Sacramento, California, 95825, United States

Location

Children's Hospital and Health Center - San Diego

San Diego, California, 92123-4282, United States

Location

Stanford Cancer Center at Stanford University Medical Center

Stanford, California, 94305, United States

Location

Children's Hospital Cancer Center

Denver, Colorado, 80218-1088, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19899, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

Baptist-South Miami Regional Cancer Program

Miami, Florida, 33176, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Emory University Hospital - Atlanta

Atlanta, Georgia, 30322, United States

Location

Cancer Research Center of Hawaii

Honolulu, Hawaii, 95813, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62794-9620, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536-0293, United States

Location

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, 04401, United States

Location

Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

C.S. Mott Children's Hospital at University of Michigan

Ann Arbor, Michigan, 48109-0238, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Spectrum Health Cancer Care - Butterworth Campus

Grand Rapids, Michigan, 49503-2560, United States

Location

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, 48910, United States

Location

Children's Hospital of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

Fairview University Medical Center - University Campus

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Ellis Fischel Cancer Center at University of Missouri - Columbia

Columbia, Missouri, 65203, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

St. Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308-1062, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Tod Children's Hospital - Forum Health

Youngstown, Ohio, 44501, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-9786, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Greenville Hospital System Cancer Center

Greenville, South Carolina, 29605, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37916, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Tech University Health Sciences Center School of Medicine

Amarillo, Texas, 79106, United States

Location

Children's Hospital of Austin

Austin, Texas, 78701, United States

Location

Driscoll Children's Hospital

Corpus Christi, Texas, 78466, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104-9958, United States

Location

Baylor University Medical Center - Houston

Houston, Texas, 77030-2399, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

INOVA Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

Carilion Cancer Center of Western Virginia

Roanoke, Virginia, 24029, United States

Location

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division

Charleston, West Virginia, 25302, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

Janeway Children's Health and Rehabilitation Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Centre Hospitalier Universitaire de Quebec

Ste-Foy, Quebec, G1V 4G2, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

MeSH Terms

Conditions

Teratoma

Interventions

Bleomycin; Filgrastim; Granulocyte Colony-Stimulating Factor; Cisplatin; Cyclophosphamide; Etoposide; etoposide phosphate; Mesna

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Marcio A. Malogolowkin, MD

  Children's Hospital Los Angeles

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2003
• First Posted: August 7, 2003
• Study Start: July 1, 2004
• Primary Completion: April 1, 2007
• Last Updated: October 17, 2013

Record last verified: 2013-10

Locations

PR (1); AU (1); US (88); CA (8)