Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill tumor cells. Giving chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial studies how well chemotherapy and radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors.

Further Study Information

OBJECTIVES:

Primary

• To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular-field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults with localized nongerminomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (CSF and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis, and fit the definition of CR/PR after second-look surgery.

• To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCGβ) ≤ 50 mIU/mL.

• To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (Germinoma) using the ALTE07C1 protocol (This objective will be assessed independently for the two strata).

Secondary

• To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6 Gy WVI and involved-field radiation therapy (IFR) focal boost to 54 Gy.

• To estimate the PFS and OS distributions of localized-germinoma patients who present with serum and/or CSF hCGβ ≤ 50 mIU/mL vs serum and/or CSF hCGβ > 50 mIU/mL and ≤ 100 mIU/mL.

OUTLINE: This is a multicenter study. Patients are stratified according to localized primary disease (nongerminomatous germ cell tumor [NGGCT] vs germinoma).

Stratum 1 (NGGCT): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 1 hour and etoposide over 1-2 hours on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive disease (complete [CR] or partial response [PR]) to induction chemotherapy undergo radiotherapy once daily (QD) 5 days a week for 6 weeks. Patients with PR, stable disease (SD), or progressive disease (PD) and normalization of tumor levels undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo radiotherapy.

Stratum 2 (Germinoma): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR undergo radiotherapy QD 5 days a week for approximately 4 weeks. Patients with PR, SD, or PD with normal tumor markers may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor during surgery undergo radiotherapy. Patients with PR or SD with residual disease (≤ 1.5 cm) and suprasellar (> 0.5 cm) or pineal (> 1 cm) involvement and normal tumor markers undergo radiotherapy after chemotherapy without second-look surgery.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, and then annually for up to 3 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Patients must be newly diagnosed with localized primary CNS nongerminomatous germ cell tumor (NGGCT) (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors (GCTs) located in the suprasellar, pineal, bifocal (pineal + suprasellar), and ventricles are eligible; tumors present in the above mentioned locations and with unifocal parenchymal extension are eligible

• Stratum 1( NGGCT): Patients must have one of the following criteria:

• Patients with serum and/or CSF hCGβ > 100 mIU/mL or any elevation of serum and CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional normal are eligible, irrespective of biopsy results

• Patients with any of the following elements on biopsy/resection are eligible, irrespective of serum and/or CSF hCGβ and AFP levels: endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma, and mixed GCT with malignant GCT elements

• Stratum 2 (Germinoma): Patients must have one of the following criteria:

• Patients with institutional normal AFP AND hCGβ 5 to ≤ 50 mIU/mL in serum and/or CSF are eligible; no histologic confirmation required

• Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus AND hCGβ ≤ 100 mIU/mL and institutional normal AFP in serum and/or CSF are eligible; no histologic confirmation required

• Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGβ ≤ 100 mIU/mL and institutional normal AFP in serum and/or CSF are eligible

• Patients must have negative lumbar CSF cytology; lumbar CSF must be obtained unless medically contraindicated

• Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123

• Patients with mature teratoma with normal tumor markers are not eligible

• Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible

• Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible

PATIENT CHARACTERISTICS:

• Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

• Platelet count ≥ 100,000/μL (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (may receive red blood cell [RBC] transfusions)

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² OR serum creatinine based on age/gender as follows:

• 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)

• 1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) and 1.4 mg/dL (female) (≥ 16 years of age)

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times ULN

• Patients with seizure disorder may be enrolled if well controlled

• Patients must not be in status, coma, or assisted ventilation prior to study enrollment

• Female patients who are pregnant are ineligible

• Lactating females are not eligible unless they have agreed not to breastfeed their infants

• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

PRIOR CONCURRENT THERAPY:

• Patients who had more than 1 prior surgery/biopsy are eligible

• Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

Ute Katherina Bartels

Principal Investigator

U.S.A.
Alabama
	Birmingham
	Children's Hospital of Alabama at University of Alabama at Birmingham
		Joseph G. Pressey	Ph: 205-939-9285
California
	Long Beach
	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
		Amanda M. Termuhlen	Ph: 562-933-8605
	Los Angeles
	Childrens Hospital Los Angeles
		Leo Mascarenhas	Ph: 323-361-2529
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph: 714-532-8636
	Palo Alto
	Lucile Packard Children's Hospital at Stanford University Medical Center
		Neyssa M. Marina	Ph: 650-723-5535
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensi	Ph: 877-827-3222
Connecticut
	Hartford
	Connecticut Children's Medical Center
		Clinical Trials Office - Connecticut Children's Medical Center	Ph: 860-545-9967
District of Columbia
	Washington
	Children's National Medical Center
		Clinical Trials Office - Children's National Medical Center	Ph: 202-884-2549
Florida
	Fort Myers
	Lee Cancer Care of Lee Memorial Health System
		Clinical Trials Office - Lee Cancer Care of Lee Memorial Healt	Ph: 877-680-0008
	Saint Petersburg
	All Children's Hospital
		Gregory A. Hale	Ph: 727-767-4176
Georgia
	Atlanta
	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
		Todd M. Cooper	Ph: 404-785-1838
Hawaii
	Honolulu
	Cancer Research Center of Hawaii
		Clinical Trials Office - Cancer Research Center of Hawaii	Ph: 808-586-2979
Illinois
	Chicago
	University of Illinois Cancer Center
		Clinical Trial Office - University of Illinois Cancer Center	Ph: 312-355-3046
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Clinical Trials Office - Cardinal Bernardin Cancer Center	Ph: 708-226-4357
Indiana
	Indianapolis
	Riley's Children Cancer Center at Riley Hospital for Children
		James M. Croop	Ph: 317-944-8784
	St. Vincent Indianapolis Hospital
		Clinical Trials Office - St. Vincent Indianapolis Hospital	Ph: 317-338-2194
Iowa
	Des Moines
	Blank Children's Hospital
		Clinical Trials Office - Blank Children's Hospital	Ph: 515-241-6729
Kentucky
	Lexington
	Lucille P. Markey Cancer Center at University of Kentucky
		Clinical Trials Office - Markey Cancer Center at University of	Ph: 859-257-3379
	Louisville
	Kosair Children's Hospital
		Clinical Trials Office - Kosair Children's Hospital	Ph: 502-629-5500
			Email: CancerResource@nortonhealthcare.org
Louisiana
	New Orleans
	Children's Hospital of New Orleans
		Clinical Trials Office - Children's Hospital of New Orleans	Ph: 504-894-5377
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce	Ph: 410-955-8804
			Email: jhcccro@jhmi.edu
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
		Carlos Rodriguez-Galindo	Ph: 617-632-4580
Michigan
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Clinical Trials Office - Barbara Ann Karmanos Cancer Institute	Ph: 313-576-9363
	Grand Rapids
	Helen DeVos Children's Hospital at Spectrum Health
		Clinical Trials Office - Helen DeVos Children's Hospital	Ph: 616-391-3050
Minnesota
	Minneapolis
	Children's Hospitals and Clinics of Minnesota - Minneapolis
		Clinical Trials Office - Children's Hospitals and Clinics of M	Ph: 612-813-5193
Missouri
	Kansas City
	Children's Mercy Hospital
		Maxine L. Hetherington	Ph: 816-234-3265
	St. Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Robert J. Hayashi	Ph: 314-454-2041
New Jersey
	Summit
	Carol G. Simon Cancer Center at Morristown Memorial Hospital
		Steven L. Halpern	Ph: 973-971-6720
New Mexico
	Albuquerque
	University of New Mexico Cancer Center
		Clinical Trials Office - University of New Mexico Cancer Cente	Ph: 505-272-6972
New York
	New York
	NYU Cancer Institute at New York University Medical Center
		Linda Granowetter	Ph: 212-263-8400
	Syracuse
	SUNY Upstate Medical University Hospital
		Clinical Trials Office - SUNY Upstate Medical University Hospi	Ph: 315-464-5476
North Carolina
	Charlotte
	Blumenthal Cancer Center at Carolinas Medical Center
		Clinical Trials Office - Blumenthal Cancer Center at Carolinas	Ph: 704-355-2884
	Presbyterian Cancer Center at Presbyterian Hospital
		Clinical Trials Office - Presbyterian Cancer Center at Presbyt	Ph: 704-384-5369
Ohio
	Columbus
	Nationwide Children's Hospital
		Laura T. Martin	Ph: 614-722-3582
	Dayton
	Dayton Children's - Dayton
		Emmett H. Broxson	Ph: 937-641-3111
Oklahoma
	Oklahoma City
	Oklahoma University Cancer Institute
		Rene Y. McNall-Knapp	Ph: 405-271-5311
Oregon
	Portland
	Knight Cancer Institute at Oregon Health and Science University
		Clinical Trials Office - Knight Cancer Institute at Oregon Hea	Ph: 503-494-1080
			Email: trials@ohsu.edu
	Legacy Emanuel Hospital and Health Center and Children's Hospital
		Clinical Trials Office - Legacy Emanuel Children's Hospital	Ph: 503-413-2560
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		Elizabeth Fox	Ph: 267-425-3010
South Carolina
	Columbia
	Palmetto Health South Carolina Cancer Center
		Clinical Trials Office - Palmetto Health South Carolina Cancer	Ph: 803-434-3680
	Greenville
	BI-LO Charities Children's Cancer Center
		Nichole L. Bryant	Ph: 864-455-8898
South Dakota
	Sioux Falls
	Sanford Cancer Center at Sanford USD Medical Center
		Clinical Trials Office - Sanford Cancer Center	Ph: 605-328-1367
Tennessee
	Memphis
	St. Jude Children's Research Hospital
		Clinical Trials Office - St. Jude Children's Research Hospital	Ph: 901-595-4644
	Nashville
	Vanderbilt-Ingram Cancer Center
		Clinical Trials Office - Vanderbilt-Ingram Cancer Center	Ph: 800-811-8480
Texas
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Clinical Trials Office - Simmons Comprehensive Cancer Center a	Ph: 866-460-4673; 214-648-7097
	Fort Worth
	Cook Children's Medical Center - Fort Worth
		Clinical Trials Office - Cook's Children's Medical Center	Ph: 682-885-2103
Utah
	Salt Lake City
	Primary Children's Medical Center
		Phillip E. Barnette	Ph: 801-662-4700
Wisconsin
	Milwaukee
	Midwest Children's Cancer Center at Children's Hospital of Wisconsin
		Michael E. Kelly	Ph: 414-456-4170
Australia
	Perth
	Princess Margaret Hospital for Children
		Catherine H. Cole	Ph: 011-6189340-8238
Canada
Ontario
	Hamilton
	McMaster Children's Hospital at Hamilton Health Sciences
		Carol Portwine	Ph: 905-521-2100x73464

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01602666
Information obtained from ClinicalTrials.gov on April 04, 2013

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