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

Extragonadal Germ Cell Tumor Clinical Trial

Official title:

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

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. 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

• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal

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