New treatment approach for children and young adults with a specific type of brain tumor
Official title: A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor
Run by Children's Oncology Group · NCT04684368 · Data updated 2026-11-12
This study is testing a new combination of chemotherapy and radiation therapy to see if it helps children and young adults with a specific type of brain tumor live longer and feel better.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 3 Years to 29 Years |
| Sex | All |
| Enrollment | 160 (estimated) |
| Sponsor | Children's Oncology Group Research network |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 170 sites (Birmingham, Alabama and 169 other locations) |
| Status | Recruiting |
| Started | July 13, 2021 |
| Main results expected | December 21, 2029 |
| Study ends | December 21, 2029 |
| Registry record updated | September 23, 2026 |
| Trial ID | NCT04684368 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are children and young adults aged 3 to 30 years with newly diagnosed localized CNS NGGCT.
✕Probably not a fit
Patients with NGGCT that has spread beyond the localized area or those with tumors originating from basal ganglia or other primary sites may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase II trial investigates a combined approach of chemotherapy and radiation therapy for children and young adults diagnosed with localized non-germinomatous germ cell tumors (NGGCT). The study aims to optimize radiation treatment for patients who respond well to initial chemotherapy, while also exploring higher dose chemotherapy for those who do not respond. Key chemotherapy agents include carboplatin, etoposide, ifosfamide, and thiotepa, which work to inhibit tumor growth. The trial will monitor progression-free survival and overall survival rates, comparing outcomes based on treatment response and radiation modality.
Why it matters
Potential benefit: If successful, this study could significantly improve survival rates and reduce the risk of spinal relapses in young patients with localized NGGCT.
How similar studies have gone: Previous studies have shown promising results with similar treatment approaches for localized NGGCT, indicating potential for success in this trial.
Who can join: the full rules
Show full inclusion / exclusion 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
Where it's running
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Providence Alaska Medical Center
Anchorage, Alaska, United States Recruiting -
Banner Children's at Desert
Mesa, Arizona, United States Recruiting -
Phoenix Childrens Hospital
Phoenix, Arizona, United States Recruiting -
Banner University Medical Center - Tucson
Tucson, Arizona, United States Recruiting -
Arkansas Children's Hospital
Little Rock, Arkansas, United States Recruiting -
Kaiser Permanente Downey Medical Center
Downey, California, United States Recruiting
Show 44 more locations
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Loma Linda University Medical Center
Loma Linda, California, United States Recruiting -
Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States Recruiting -
Children's Hospital Los Angeles
Los Angeles, California, United States Recruiting -
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, United States Recruiting -
Cedars-Sinai Medical Center
Los Angeles, California, United States Recruiting -
Valley Children's Hospital
Madera, California, United States Recruiting -
Kaiser Permanente-Oakland
Oakland, California, United States Recruiting -
Children's Hospital of Orange County
Orange, California, United States Recruiting -
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States Recruiting -
Rady Children's Hospital - San Diego
San Diego, California, United States Recruiting -
UCSF Medical Center-Mission Bay
San Francisco, California, United States Recruiting -
Children's Hospital Colorado
Aurora, Colorado, United States Recruiting -
Connecticut Children's Medical Center
Hartford, Connecticut, United States Recruiting -
Smilow Cancer Center/Yale-New Haven Hospital
New Haven, Connecticut, United States Recruiting -
Yale University
New Haven, Connecticut, United States Recruiting -
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States Recruiting -
Children's National Medical Center
Washington D.C., District of Columbia, United States Recruiting -
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States Recruiting -
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States Recruiting -
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States Recruiting -
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States Recruiting -
Nicklaus Children's Hospital
Miami, Florida, United States Recruiting -
Arnold Palmer Hospital for Children
Orlando, Florida, United States Recruiting -
Nemours Children's Hospital
Orlando, Florida, United States Recruiting -
Nemours Children's Clinic - Pensacola
Pensacola, Florida, United States Recruiting -
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States Recruiting -
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States Recruiting -
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States Recruiting -
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States Recruiting -
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States Recruiting -
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States Recruiting -
University of Illinois
Chicago, Illinois, United States Recruiting -
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States Recruiting -
Loyola University Medical Center
Maywood, Illinois, United States Recruiting -
OSF Children's Hospital of Illinois
Peoria, Illinois, United States Recruiting -
Riley Hospital for Children
Indianapolis, Indiana, United States Recruiting -
Blank Children's Hospital
Des Moines, Iowa, United States Recruiting -
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States Recruiting -
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States Recruiting -
Norton Children's Hospital
Louisville, Kentucky, United States Recruiting -
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States Recruiting -
Eastern Maine Medical Center
Bangor, Maine, United States Recruiting -
Maine Children's Cancer Program
Scarborough, Maine, United States Recruiting -
Sinai Hospital of Baltimore
Baltimore, Maryland, United States Recruiting
+120 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Principal investigator: Shannon M MacDonald — Children's Oncology Group
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Monitoring and treating germ cell tumors in children and adults
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.