Clinical trial NCT00467051: Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors
Official title: Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Childhood Extracranial Germ Cell Tumor
Childhood Extragonadal Malignant Germ Cell Tumor
Childhood Malignant Ovarian Germ Cell Tumor
Childhood Malignant Testicular Germ Cell Tumor
Ovarian Choriocarcinoma
Ovarian Embryonal Carcinoma
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 Yolk Sac Tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-27
Enrollment: 20
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
timeFrame: At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days)
Secondary outcomes:
measure: The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.
timeFrame: Two cycles of chemotherapy; expected to be 42 days of treatment.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Medical Center-University Campus
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Kaiser Permanente Downey Medical Center
state: California
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: Torrance
country: United States
facility: Harbor-University of California at Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic - Pensacola
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: New York
country: United States
facility: Columbia University/Herbert Irving Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic Children's Hospital
state: Virginia
city: Charleston
country: United States
facility: West Virginia University Charleston Division
state: West Virginia
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: San Juan
country: Puerto Rico
facility: San Jorge Children's Hospital
Study officials:
affiliation: Children's Oncology Group
name: Carlos Rodriguez-Galindo
role: PRINCIPAL_INVESTIGATOR
References: