Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

Recurrent Ovarian Germ Cell Tumor Clinical Trial

Official title:

Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00467051
• Other study ID #: AGCT0521
• Secondary ID: NCI-2009-00374CO
• Status: Completed
• Phase: Phase 2
• Start date: November 5, 2007
• Est. completion date: June 30, 2018

Study information

• Verified date: October 2017
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial is studying how well giving combination chemotherapy works in treating young patients with recurrent or resistant malignant germ cell tumors. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Description:

PRIMARY OBJECTIVES:

I. Determine the response rate in pediatric patients with recurrent or resistant malignant germ cell tumors (GCT) treated with paclitaxel, ifosfamide, and carboplatin.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this regimen in these patients. II. To Collect tissue for the tumor bank that will aid in the identification of the biological characteristics of recurrent GCT.

OUTLINE: This is a multicenter study.

Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood count returns to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 30, 2018
• Est. primary completion date: March 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Histologically confirmed (at original diagnosis) extracranial germ cell tumor (GCT) containing 1 of the following malignant elements:

• Yolk sac tumor (endodermal sinus tumor)

• Choriocarcinoma

• Embryonal carcinoma

• Meets 1 of the following disease criteria:

• Recurrent malignant disease

• Chemotherapy-resistant disease

• Relapsed disease

• Disease refractory to conventional therapy

• Measurable disease

• Must have received a prior first-line chemotherapy regimen that included cisplatin

• Patients with tumor marker (AFP and/or BHCG) elevation alone or bone scan findings alone are not eligible*

• Patients with immature teratoma (any grade), germinoma, sex-cord stromal tumors, or recurrent GCT previously treated with surgery alone are not eligible

• Karnofsky performance status (PS) 50-100% (age > 16 years) OR Lansky PS 50-100% (age = 16 years) OR ECOG PS 0-2

• Life expectancy = 8 weeks

• Absolute neutrophil count = 750/mm³

• Platelet count = 75,000/mm³ (transfusion independent)

• Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min OR creatinine normal based on age/gender, as defined by the following:

• = 0.4 mg/dL (1 month to < 6 months of age)

• = 0.5 mg/dL (6 months to < 1 year of age)

• = 0.6 mg/dL (1 to < 2 years of age)

• = 0.8 mg/dL (2 to < 6 years of age)

• = 1.0 mg/dL (6 to < 10 years of age)

• = 1.2 mg/dL (10 to < 13 years of age)

• = 1.4 mg/dL (13 to = 16 years of age) (female)

• = 1.5 mg/dL (13 to < 16 years of age) (male)

• = 1.7 mg/dL (= 16 years of age) (male)

• Bilirubin = 1.5 times upper limit of normal (ULN) for age

• ALT < 2.5 times ULN for age

• Shortening fraction = 27% by echocardiogram OR ejection fraction = 50% by gated radionuclide study

• No dyspnea at rest

• No exercise intolerance

• Pulse oximetry > 94% (if there is clinical indication for determination)

• Patients with seizure disorder are eligible provided they are on non-enzyme inducing anticonvulsants and seizures are well controlled

• No CNS toxicity > grade 2

• No active graft-versus-host disease

• No allergy to Cremophor EL or castor oil

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other concurrent chemotherapy or immunomodulating agents

• Recovered from prior chemotherapy, immunotherapy, or radiotherapy

• At least 1 week since prior growth factors (2 weeks for pegfilgrastim)

• At least 1 week since prior biologic therapy

• At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea)

• At least 2 weeks since prior local palliative radiotherapy (i.e., small port)

• At least 6 months since prior craniospinal radiotherapy or radiotherapy to = 50% of pelvis

• At least 6 weeks since other prior substantial bone marrow radiotherapy

• At least 6 months since prior allogeneic stem cell transplantation

• Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated

Related Conditions & MeSH terms

• Carcinoma
• Childhood Extracranial Germ Cell Tumor
• Childhood Extragonadal Malignant Germ Cell Tumor
• Childhood Malignant Ovarian Germ Cell Tumor
• Childhood Malignant Testicular Germ Cell Tumor
• Choriocarcinoma
• Germinoma
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Ovarian Choriocarcinoma
• Ovarian Embryonal Carcinoma
• Ovarian Neoplasms
• Ovarian Yolk Sac Tumor
• Recurrent Childhood Malignant Germ Cell Tumor
• Recurrent Malignant Testicular Germ Cell Tumor
• Recurrent Ovarian Germ Cell Tumor
• Testicular Choriocarcinoma
• Testicular Embryonal Carcinoma
• Testicular Mixed Choriocarcinoma and Embryonal Carcinoma
• Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
• Testicular Mixed Embryonal Carcinoma and Yolk Sac Tumor
• Testicular Neoplasms
• Testicular Yolk Sac Tumor

Intervention

Drug:
• Carboplatin
Given IV

Biological:
• Filgrastim
Given IV or subcutaneously

Drug:
• Ifosfamide
Given IV

Other:
• Laboratory Biomarker Analysis
Optional correlative studies

Drug:
• Paclitaxel
Given IV

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	San Jorge Children's Hospital	San Juan
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	University of Connecticut	Farmington	Connecticut
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Miller Children's and Women's Hospital Long Beach	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University/Herbert Irving Cancer Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Florida Hospital Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Carilion Clinic Children's Hospital	Roanoke	Virginia
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
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	UCSF Medical Center-Mount Zion	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	California
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Harbor-University of California at Los Angeles Medical Center	Torrance	California
United States	The University of Arizona Medical Center-University Campus	Tucson	Arizona
United States	Children's National Medical Center	Washington	District of Columbia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware

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	Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	Patients who demonstrate a PR or CR, as defined below, will be considered as responders. RECIST criteria: CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet above criteria.	At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days)
Secondary	The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.		Two cycles of chemotherapy; expected to be 42 days of treatment.