RECRUITING Phase 2 ClinicalTrials.gov

A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT

Sponsor: Children's Oncology Group • ClinicalTrials.gov ID: NCT04684368

Registry updated: 2026-09-23

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Description

This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.

Interventions

Biospecimen Collection (Procedure)
Undergo collection of CSF and blood samples
Carboplatin (Drug)
Given IV
Etoposide (Drug)
Given IV
Filgrastim (Biological)
Given subcutaneously (SC) or IV
Ifosfamide (Drug)
Given IV
Magnetic Resonance Imaging (Procedure)
Undergo MRI
Mesna (Drug)
Given IV or orally
Pegfilgrastim (Biological)
Given SC
Peripheral Blood Stem Cell Transplantation (Procedure)
Undergo PBSC transplant
Questionnaire Administration (Other)
Ancillary studies
Radiation Therapy (Radiation)
Undergo WVSCI radiation therapy
Radiation Therapy (Radiation)
Undergo Craniospinal radiation therapy
Second-Look Surgery (Procedure)
Undergo second-look surgery if needed
Thiotepa (Drug)
Given IV

Eligibility criteria

Inclusion Criteria: * Patients must be \>= 3 years and \< 30 years at the time of study enrollment * Patients must be newly diagnosed with localized primary CNS NGGCT of the suprasellar and/or pineal region by pathology and/or serum or cerebrospinal fluid (CSF) elevation of AFP above institutional normal or \> 10 ng/mL or human chorionic gonadotropin (hCG) beta \> 100 mIU/mL as confirmed by Rapid Central Marker Screening Review on APEC14B1-CNS. Suprasellar, pineal and bifocal tumors are included. (CSF tumor markers and cytology must be within 31 days prior to enrollment and start of protocol therapy \[repeat if necessary\]. Serum tumor markers, AFP and hCGbeta must be within 7 days prior to enrollment and start of protocol therapy \[repeat if necessary\]). Basal ganglia or other primary sites are excluded * Patients with any of the following pathological elements are eligible: endodermal sinus (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma and mixed germ cell tumor (GCT) (i.e., may include some pure germinoma) if malignant elements listed above are present. Patients with only mature teratoma are excluded. Patients with pure germinoma admixed with mature teratoma are excluded (would be eligible for pure germinoma protocols) * Patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment. If surgical resection is performed, patients must have pre-operative and post operative brain MRI with and without gadolinium. Note: The post operative brain MRI should be obtained within 72 hours of surgery. If patient has a biopsy only, post-operative brain MRI is recommended but not required (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment) * Patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment. Spine MRI with and without gadolinium is recommended (within 31 days prior to study enrollment and start of protocol therapy - Note: for patients that have had surgery and post-operative imaging performed, it is the post-operative MRI following definitive surgery that must be obtained within 31 days prior to enrollment) * Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. Note: False positive cytology can occur within 10 days of surgery. If lumbar CSF for cytology is not performed prior to surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. Patients with negative CSF cytology from lumbar puncture obtained 1 to 10 days after surgery do not need cytology repeated * Patients must have RAPID CENTRAL TUMOR MARKER REVIEW CSF tumor markers obtained prior to enrollment unless medically contraindicated. Ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred. In case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first * Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment) * Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment) * Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment) * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/sex as follows (within 7 days prior to enrollment): * Age: Maximum serum creatinine (mg/dL) * 3 to \< 6 years: 0.8 (male), 0.8 (female) * 6 to \< 10 years: 1 (male), 1 (female) * 10 to \< 13 years: 1.2 (male), 1.2 (female) * 13 to \< 16 years: 1.5 (male), 1.4 (female) * \>= 16 years: male (1.7), 1.4 (female) * Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) * Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment) * Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L * Central nervous system function defined as: * Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled * Patients must not be in status epilepticus, coma or assisted ventilation prior to study enrollment * Protocol therapy must begin within 31 calendar days of definitive surgery or clinical diagnosis, whichever is later. If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery. * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met * NEUROCOGNITIVE FUNCTION AND QUALITY OF LIFE ASSESSMENT: * English-, Spanish-, or French- speaking * Note: Patients who speak a language other than English, Spanish, or French will be allowed to participate in ACNS2021 but will not complete the neurocognitive and quality of life assessments * No known history of neurodevelopmental disorder prior to diagnosis of NGGCT (e.g., Down syndrome, fragile X, William syndrome, intellectual disability). Patients with NF1 will be allowed to participate * Additional eligibility criteria for the COG Standardized Neuropsychological Battery only: must be at a site that has a psychologist to administer the battery * Note: If not eligible for the COG Standardized Battery, patients should still complete the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Pediatric Quality of Life Inventory (PedsQL), Adaptive Behavior Assessment System Third Edition (ABAS-3), and Behavior Assessment System for Children, Third Edition (BASC-3) questionnaires Exclusion Criteria: * Patients with tumors located outside the ventricles (i.e., basal ganglia, thalamus) * Patients with only mature teratoma and non-elevated markers upon tumor sampling at diagnosis * Patients who have received any prior tumor-directed therapy for their diagnosis of NGGCT other than surgical intervention and corticosteroids * Patients with metastatic disease (i.e., MRI evaluation, lumbar CSF cytology or intraoperative evidence of dissemination) * Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs * Note: Serum and urine pregnancy tests may be falsely positive due to HCGbeta-secreting germ cell tumors. Ensure the patient is not pregnant by institutional standards * Lactating females who plan to breastfeed their infants * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Conditions

Central Nervous System Nongerminomatous Germ Cell Tumor Choriocarcinoma Embryonal Carcinoma Immature Teratoma Malignant Teratoma Mixed Germ Cell Tumor Pineal Region Germ Cell Tumor Pineal Region Immature Teratoma Pineal Region Yolk Sac Tumor Suprasellar Germ Cell Tumor

Locations

Children's Hospital of Alabama — Birmingham, Alabama, United States
Providence Alaska Medical Center — Anchorage, Alaska, United States
Banner Children's at Desert — Mesa, Arizona, United States
Phoenix Childrens Hospital — Phoenix, Arizona, United States
Banner University Medical Center - Tucson — Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
Arkansas Children's Hospital — Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center — Downey, California, United States
Loma Linda University Medical Center — Loma Linda, California, United States
Miller Children's and Women's Hospital Long Beach — Long Beach, California, United States
Children's Hospital Los Angeles — Los Angeles, California, United States
Kaiser Permanente Los Angeles Medical Center — Los Angeles, California, United States
Cedars-Sinai Medical Center — Los Angeles, California, United States
Valley Children's Hospital — Madera, California, United States
Kaiser Permanente-Oakland — Oakland, California, United States
Children's Hospital of Orange County — Orange, California, United States
Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
Rady Children's Hospital - San Diego — San Diego, California, United States
UCSF Medical Center-Mission Bay — San Francisco, California, United States
Children's Hospital Colorado — Aurora, Colorado, United States
Connecticut Children's Medical Center — Hartford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
Yale University — New Haven, Connecticut, United States
Alfred I duPont Hospital for Children — Wilmington, Delaware, United States
Children's National Medical Center — Washington D.C., District of Columbia, United States
Golisano Children's Hospital of Southwest Florida — Fort Myers, Florida, United States
UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville — Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
Nicklaus Children's Hospital — Miami, Florida, United States
Arnold Palmer Hospital for Children — Orlando, Florida, United States
Nemours Children's Hospital — Orlando, Florida, United States
Nemours Children's Clinic - Pensacola — Pensacola, Florida, United States
Sacred Heart Hospital — Pensacola, Florida, United States
Johns Hopkins All Children's Hospital — St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa — Tampa, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children — Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States
Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
University of Illinois — Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
Loyola University Medical Center — Maywood, Illinois, United States
OSF Children's Hospital of Illinois — Peoria, Illinois, United States
Riley Hospital for Children — Indianapolis, Indiana, United States
Blank Children's Hospital — Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
University of Kentucky/Markey Cancer Center — Lexington, Kentucky, United States
Norton Children's Hospital — Louisville, Kentucky, United States
Ochsner Medical Center Jefferson — New Orleans, Louisiana, United States
Eastern Maine Medical Center — Bangor, Maine, United States
Maine Children's Cancer Program — Scarborough, Maine, United States
Sinai Hospital of Baltimore — Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
C S Mott Children's Hospital — Ann Arbor, Michigan, United States
Children's Hospital of Michigan — Detroit, Michigan, United States
Michigan State University — East Lansing, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital — Grand Rapids, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital — Grand Rapids, Michigan, United States
Corewell Health Children's — Royal Oak, Michigan, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis — Minneapolis, Minnesota, United States
Mayo Clinic in Rochester — Rochester, Minnesota, United States
University of Mississippi Medical Center — Jackson, Mississippi, United States
University of Missouri Children's Hospital — Columbia, Missouri, United States
Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
Cardinal Glennon Children's Medical Center — St Louis, Missouri, United States
Washington University School of Medicine — St Louis, Missouri, United States
Mercy Hospital Saint Louis — St Louis, Missouri, United States
Children's Hospital and Medical Center of Omaha — Omaha, Nebraska, United States
University of Nebraska Medical Center — Omaha, Nebraska, United States
Oncology Las Vegas - Henderson — Henderson, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation — Las Vegas, Nevada, United States
Renown Regional Medical Center — Reno, Nevada, United States
Cancer Care Specialists - Reno — Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center — Lebanon, New Hampshire, United States
Hackensack University Medical Center — Hackensack, New Jersey, United States
Morristown Medical Center — Morristown, New Jersey, United States
Saint Peter's University Hospital — New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital — New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center — Newark, New Jersey, United States
Saint Joseph's Regional Medical Center — Paterson, New Jersey, United States
Albany Medical Center — Albany, New York, United States
Maimonides Medical Center — Brooklyn, New York, United States
Roswell Park Cancer Institute — Buffalo, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York — New Hyde Park, New York, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone — New York, New York, United States
Memorial Sloan Kettering Cancer Center — New York, New York, United States
University of Rochester — Rochester, New York, United States
Stony Brook University Medical Center — Stony Brook, New York, United States
State University of New York Upstate Medical University — Syracuse, New York, United States
Montefiore Medical Center-Einstein Campus — The Bronx, New York, United States
Montefiore Medical Center - Moses Campus — The Bronx, New York, United States
New York Medical College — Valhalla, New York, United States
Carolinas Medical Center/Levine Cancer Institute — Charlotte, North Carolina, United States
Duke University Medical Center — Durham, North Carolina, United States
East Carolina University — Greenville, North Carolina, United States
Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
Sanford Broadway Medical Center — Fargo, North Dakota, United States
Children's Hospital Medical Center of Akron — Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
Rainbow Babies and Childrens Hospital — Cleveland, Ohio, United States
Cleveland Clinic Foundation — Cleveland, Ohio, United States
Nationwide Children's Hospital — Columbus, Ohio, United States
Dayton Children's Hospital — Dayton, Ohio, United States
ProMedica Flower Hospital — Sylvania, Ohio, United States
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital — Toledo, Ohio, United States
University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
Legacy Emanuel Children's Hospital — Portland, Oregon, United States
Oregon Health and Science University — Portland, Oregon, United States
Lehigh Valley Hospital-Cedar Crest — Allentown, Pennsylvania, United States
Geisinger Medical Center — Danville, Pennsylvania, United States
Penn State Children's Hospital — Hershey, Pennsylvania, United States
Saint Christopher's Hospital for Children — Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
Rhode Island Hospital — Providence, Rhode Island, United States
Medical University of South Carolina — Charleston, South Carolina, United States
Prisma Health Richland Hospital — Columbia, South Carolina, United States
BI-LO Charities Children's Cancer Center — Greenville, South Carolina, United States
Prisma Health Cancer Institute - Faris — Greenville, South Carolina, United States
Sanford USD Medical Center - Sioux Falls — Sioux Falls, South Dakota, United States
East Tennessee Childrens Hospital — Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial — Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas — Austin, Texas, United States
Driscoll Children's Hospital — Corpus Christi, Texas, United States
Medical City Dallas Hospital — Dallas, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas — Dallas, Texas, United States
El Paso Children's Hospital — El Paso, Texas, United States
Cook Children's Medical Center — Fort Worth, Texas, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center — Houston, Texas, United States
UT MD Anderson Cancer Center — Houston, Texas, United States
Children's Hospital of San Antonio — San Antonio, Texas, 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
Scott and White Memorial Hospital — Temple, Texas, United States
Primary Children's Hospital — Salt Lake City, Utah, United States
University of Vermont and State Agricultural College — Burlington, Vermont, United States
University of Virginia Cancer Center — Charlottesville, Virginia, United States
Children's Hospital of The King's Daughters — Norfolk, Virginia, United States
VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
Carilion Children's — Roanoke, Virginia, United States
Seattle Children's Hospital — Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital — Spokane, Washington, United States
Mary Bridge Children's Hospital and Health Center — Tacoma, Washington, United States
Madigan Army Medical Center — Tacoma, Washington, United States
West Virginia University Healthcare — Morgantown, West Virginia, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center — Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield — Marshfield, Wisconsin, United States
Sydney Children's Hospital — Randwick, New South Wales, Australia
The Children's Hospital at Westmead — Westmead, New South Wales, Australia
Queensland Children's Hospital — South Brisbane, Queensland, Australia
Women's and Children's Hospital-Adelaide — North Adelaide, South Australia, Australia
Royal Children's Hospital — Parkville, Victoria, Australia
Perth Children's Hospital — Perth, Western Australia, Australia
Alberta Children's Hospital — Calgary, Alberta, Canada
University of Alberta Hospital — Edmonton, Alberta, Canada
British Columbia Children's Hospital — Vancouver, British Columbia, Canada
CancerCare Manitoba — Winnipeg, Manitoba, Canada
IWK Health Centre — Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences — Hamilton, Ontario, Canada
Hospital for Sick Children — Toronto, Ontario, Canada
The Montreal Children's Hospital of the MUHC — Montreal, Quebec, Canada
Centre Hospitalier Universitaire Sainte-Justine — Montreal, Quebec, Canada
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont — Sherbrooke, Quebec, Canada
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL) — Québec, Canada
Christchurch Hospital — Christchurch, New Zealand

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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

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