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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00066482
Other study ID # AGCT01P1
Secondary ID CDR0000316244
Status Completed
Phase N/A
First received August 6, 2003
Last updated October 15, 2013
Start date July 2004

Study information

Verified date October 2013
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 19
Est. completion date
Est. primary completion date April 2007
Accepts healthy volunteers No
Gender Both
Age group N/A to 21 Years
Eligibility 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

Study Design

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


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Australia Princess Margaret Hospital for Children Perth Western Australia
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Hopital Sainte Justine Montreal Quebec
Canada Montreal Children's Hospital at McGill University Health Center Montreal Quebec
Canada Allan Blair Cancer Centre at Pasqua Hospital Regina Saskatchewan
Canada Janeway Children's Health and Rehabilitation Centre St. John's Newfoundland and Labrador
Canada Centre Hospitalier Universitaire de Quebec Ste-Foy Quebec
Canada Hospital for Sick Children Toronto Ontario
Canada Children's & Women's Hospital of British Columbia Vancouver British Columbia
Puerto Rico San Jorge Children's Hospital Santurce
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Texas Tech University Health Sciences Center School of Medicine Amarillo Texas
United States C.S. Mott Children's Hospital at University of Michigan Ann Arbor Michigan
United States Emory University Hospital - Atlanta Atlanta Georgia
United States Children's Hospital of Austin Austin Texas
United States Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore Maryland
United States CancerCare of Maine at Eastern Maine Medial Center Bangor Maine
United States Comprehensive Cancer Center at University of Alabama at Birmingham Birmingham Alabama
United States Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston Massachusetts
United States Albert Einstein Cancer Center at Albert Einstein College of Medicine Bronx New York
United States Hollings Cancer Center at Medical University of South Carolina Charleston South Carolina
United States West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division Charleston West Virginia
United States Blumenthal Cancer Center at Carolinas Medical Center Charlotte North Carolina
United States Presbyterian Cancer Center at Presbyterian Hospital Charlotte North Carolina
United States Children's Memorial Hospital - Chicago Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia Missouri
United States Driscoll Children's Hospital Corpus Christi Texas
United States Medical City Dallas Hospital Dallas Texas
United States Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas Texas
United States Children's Medical Center - Dayton Dayton Ohio
United States Children's Hospital Cancer Center Denver Colorado
United States Barbara Ann Karmanos Cancer Institute Detroit Michigan
United States Southern California Permanente Medical Group Downey California
United States Duke Comprehensive Cancer Center Durham North Carolina
United States INOVA Fairfax Hospital Fairfax Virginia
United States Hurley Medical Center Flint Michigan
United States Lee Cancer Care of Lee Memorial Health System Fort Myers Florida
United States Cook Children's Medical Center - Fort Worth Fort Worth Texas
United States University of Florida Shands Cancer Center Gainesville Florida
United States Spectrum Health Cancer Care - Butterworth Campus Grand Rapids Michigan
United States St. Vincent Hospital Regional Cancer Center Green Bay Wisconsin
United States Greenville Hospital System Cancer Center Greenville South Carolina
United States Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods Michigan
United States Hackensack University Medical Center Cancer Center Hackensack New Jersey
United States Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania
United States Cancer Research Center of Hawaii Honolulu Hawaii
United States Baylor University Medical Center - Houston Houston Texas
United States M.D. Anderson Cancer Center at University of Texas Houston Texas
United States St. Vincent Indianapolis Hospital Indianapolis Indiana
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic Jacksonville Florida
United States Children's Mercy Hospital Kansas City Missouri
United States Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City Kansas
United States East Tennessee Children's Hospital Knoxville Tennessee
United States Breslin Cancer Center at Ingham Regional Medical Center Lansing Michigan
United States Markey Cancer Center at University of Kentucky Chandler Medical Center Lexington Kentucky
United States Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock Arkansas
United States St. Barnabas Medical Center Livingston New Jersey
United States Loma Linda University Cancer Institute at Loma Linda University Medical Center Loma Linda California
United States Children's Hospital Los Angeles Los Angeles California
United States Covenant Children's Hospital Lubbock Texas
United States Children's Hospital Central California Madera California
United States University of Wisconsin Comprehensive Cancer Center Madison Wisconsin
United States Marshfield Clinic - Marshfield Center Marshfield Wisconsin
United States St. Jude Children's Research Hospital Memphis Tennessee
United States Baptist-South Miami Regional Cancer Program Miami Florida
United States Miami Children's Hospital Miami Florida
United States University of Miami Sylvester Comprehensive Cancer Center Miami Florida
United States Midwest Children's Cancer Center Milwaukee Wisconsin
United States Children's Hospital of Minnesota - Minneapolis Minneapolis Minnesota
United States Fairview University Medical Center - University Campus Minneapolis Minnesota
United States Oklahoma University Medical Center Oklahoma City Oklahoma
United States Children's Hospital of Orange County Orange California
United States Sacred Heart Cancer Center at Sacred Heart Hospital Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States St. Christopher's Hospital for Children Philadelphia Pennsylvania
United States Phoenix Children's Hospital Phoenix Arizona
United States Carilion Cancer Center of Western Virginia Roanoke Virginia
United States James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York
United States Mayo Clinic Cancer Center Rochester Minnesota
United States Kaiser Permanente Medical Center - Oakland Sacramento California
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 Children's Hospital and Health Center - San Diego San Diego California
United States Southern Illinois University School of Medicine Springfield Illinois
United States Siteman Cancer Center at Barnes-Jewish Hospital St. Louis Missouri
United States All Children's Hospital St. Petersburg Florida
United States Stanford Cancer Center at Stanford University Medical Center Stanford California
United States SUNY Upstate Medical University Hospital Syracuse New York
United States St. Joseph's Cancer Institute at St. Joseph's Hospital Tampa Florida
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States Kaplan Cancer Center at St. Mary's Medical Center West Palm Beach Florida
United States Alfred I. duPont Hospital for Children Wilmington Delaware
United States Tod Children's Hospital - Forum Health Youngstown Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Puerto Rico, 

Outcome

Type Measure Description Time frame Safety issue
Primary Feasibility of adding cyclophosphamide to a PEB backbone 2 years No
Secondary Maximum tolerated dose 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). 21 days Yes
Secondary Estimate the response rate To estimate the response rate in this group of patients to a regimen of cyclophosphamide combined with cisplatin, etoposide, bleomycin (C-PEB). Length of study No
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