Combination Chemotherapy Plus Amifostine in Treating Children With Malignant Germ Cell Tumors

Ovarian Cancer Clinical Trial

Official title:

High-Dose Cisplatin, Etoposide and Bleomycin (HD-PEB) Combined With Amifostine in Children With High-Risk Malignant Germ Cell Tumors - A POG Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003811
• Other study ID #: 9749
• Secondary ID: POG-9749CDR00000
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: July 3, 2013
• Start date: April 2000
• Est. completion date: September 2007

Study information

• Verified date: July 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: Chemotherapy drugs use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of high-dose cisplatin, etoposide, and bleomycin plus amifostine in treating children who have malignant germ cell tumors.

Description:

OBJECTIVES: I. Evaluate the early efficacy and toxicity profile of high-dose cisplatin, etoposide, bleomycin, and amifostine in children with newly diagnosed, high-risk malignant, extragonadal germ cell tumors. II. Determine whether the use of amifostine can reduce the hematologic and nonhematologic toxic effects of this combination chemotherapy in these patients when compared to similar patients treated on POG-9049/CCG-8881 with the same combination chemotherapy. III. Determine the response rate of patients treated with this regimen.

OUTLINE: Patients undergo surgical biopsy or resection. Patients then receive bleomycin IV over 10 minutes on day 1 and etoposide IV over 1 hour, amifostine IV over 15 minutes, and cisplatin IV over 1 hour on days 1-5. Treatment repeats every 3-4 weeks for 4 courses in the absence of unacceptable toxicity or disease progression. Patients who have no disease after 4 courses of chemotherapy receive no further treatment. Patients who have residual disease undergo second-look surgery. After surgery, patients who still have active tumor receive 2 additional courses of chemotherapy. Those patients who still have tumor after the 2 additional courses may have a third surgery. Patients are followed every month for 6 months, every 2 months for 6 months, every 6 months for 1 year, and then annually thereafter until death.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 1.39 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 2007
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 14 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically confirmed, newly diagnosed, high-risk, extracranial germ cell tumors including the following: Yolk sac carcinoma (endodermal sinus tumor) Embryonal carcinoma Choriocarcinoma Teratoma with mixed malignant elements (malignant teratoma) OR Malignant recurrence (stage III or IV) of previously resected stage I extracranial, extragonadal tumor High-risk disease defined as stage III or IV extragonadal tumors Measurable disease by diagnostic imaging

PATIENT CHARACTERISTICS: Age: Under 15 at time of diagnosis Performance status: Not specified Life expectancy: Not specified Hematopoietic: Absolute neutrophil count greater than 750/mm3 Platelet count greater than 75,000/mm3 Hepatic: Not specified Renal: Creatinine normal OR Glomerular filtration rate at least 50% of normal

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

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Germ Cell Tumor
• Drug/Agent Toxicity by Tissue/Organ
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Ovarian Cancer

Intervention

Biological:
• bleomycin sulfate

Drug:
• amifostine trihydrate

• cisplatin

• etoposide

Procedure:
• conventional surgery

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Children's Hospital	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Clinique de Pediatrie	Geneva
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Mission Saint Joseph's Health System	Asheville	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Medical School-Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John's Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	University of California San Diego Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Walt Disney Memorial Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Maine Children's Cancer Program	Portland	Maine
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Massey Cancer Center	Richmond	Virginia
United States	Carilion Roanoke Community Hospital	Roanoke	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	MBCCOP - South Texas Pediatric	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	California
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Naval Medical Center - San Diego	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Stanford University Medical Center	Stanford	California
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Florida Pediatric	Tampa	Florida
United States	Scott and White Clinic	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

References & Publications (1)

Marina N, Chang KW, Malogolowkin M, London WB, Frazier AL, Womer RB, Rescorla F, Billmire DF, Davis MM, Perlman EJ, Giller R, Lauer SJ, Olson TA; Children's Oncology Group. Amifostine does not protect against the ototoxicity of high-dose cisplatin combine — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility from Efficacy Standpoint	The hazard rate is constant over 1.39 years, then the probability of the occurrence of a failure within this time interval follows a Poisson distribution. The table below shows the trial feasibility probabilities associated with those failure rates. We define the probability of feasibility as the probability of observing a total of at most less than three failures in 25 patient years of follow-up.		No
Secondary	Assessment of Reduction in Toxicity	Descriptive statistics will be performed for nephrotoxicity, hematologic and pulmonary toxicities, and inference will be performed for ototoxicity. Frequency tables of the occurrences of toxicities by grade will be tabulated for ANC and platelets. To assess nephrotoxicity and pulmonary toxicity, descriptive statistics will be calculated for GFR and DLCO, respectively. These statistics will be compared to the corresponding summaries on the appropriate population of patients from POG 9049/CCG 8881.		No