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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00066482
First received: August 6, 2003
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Biological: bleomycin sulfate
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: etoposide
Procedure: conventional surgery
Biological: MESNA

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Cisplatin, Etoposide, Bleomycin and Escalating Dose Cyclophosphamide Therapy for Children With High Risk Malignant Germ Cell Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Feasibility of adding cyclophosphamide to a PEB backbone [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB) in previously untreated children with high-risk malignant germ cell tumors (MGCT).

  • Estimate the response rate [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB).


Enrollment: 19
Study Start Date: July 2004
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: combination chemotherapy

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
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)
Other Names:
  • BLEO
  • BLM
  • Blenoxane
  • NSC #125066
Biological: filgrastim
Given SQ once daily 5 micrograms/kg/dose Starting on Day 6 (Week 1, 4, 7, 10) Daily until ANC > 5,000/uL
Other Names:
  • GRANULOCYTE COLONY-STIMULATING FACTOR
  • r-metHuG-CSF
  • G-CSF
  • Filgrastim
  • Neupogen
  • NSC #614629
Drug: cisplatin
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)
Other Names:
  • Cis-diamminedichloroplatinum II
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
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)
Other Names:
  • Cytoxan
  • NSC #026271
Drug: etoposide
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)
Other Names:
  • VP-16
  • VePesid
  • Etopophos
  • NSC #141540
Procedure: conventional surgery
Stage III/IV extragonadal tumors: biopsy followed by a definitive surgical excision after maximal chemotherapy effect, likely after 4 cycles of therapy
Biological: MESNA
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.
Other Names:
  • sodium 2-mercaptoethane sulfonate
  • Mesnex
  • NSC #113891

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066482

  Hide Study Locations
Locations
United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93638-8762
Children's Hospital of Orange County
Orange, California, United States, 92868
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States, 95825
Children's Hospital and Health Center - San Diego
San Diego, California, United States, 92123-4282
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218-1088
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Baptist-South Miami Regional Cancer Program
Miami, Florida, United States, 33176
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Miami Children's Hospital
Miami, Florida, United States, 33155
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
All Children's Hospital
St. Petersburg, Florida, United States, 33701
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States, 48109-0238
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Hurley Medical Center
Flint, Michigan, United States, 48503
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
United States, Minnesota
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
St. Barnabas Medical Center
Livingston, New Jersey, United States, 07039
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States, 44501
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134-1095
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States, 29605
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States, 79106
Children's Hospital of Austin
Austin, Texas, United States, 78701
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78466
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Virginia
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Carilion Cancer Center of Western Virginia
Roanoke, Virginia, United States, 24029
United States, West Virginia
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
United States, Wisconsin
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Newfoundland and Labrador
Janeway Children's Health and Rehabilitation Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Marcio A. Malogolowkin, MD Children's Hospital Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00066482     History of Changes
Other Study ID Numbers: AGCT01P1, CDR0000316244
Study First Received: August 6, 2003
Last Updated: October 15, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
childhood teratoma
childhood extragonadal germ cell tumor

Additional relevant MeSH terms:
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Mesna
Bleomycin
Etoposide phosphate
Cisplatin
Cyclophosphamide
Etoposide
Lenograstim
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 26, 2014