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NCT04684368From ClinicalTrials.govRecruiting

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

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

  • 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

At a glance

Phase
Phase 2
Study type
Interventional
Sponsor
Children's Oncology Group
Enrolment target
160
Started
13 July 2021
Main results due
21 December 2029
Study sites
170
Registry updated
23 September 2026

Can you take part?

  • Ages 3 years to 29 years.
  • Open to any sex.
  • You need the condition being studied — healthy volunteers are not accepted.

These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.

Read the full 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

What this study is about

In the sponsor’s own words, from the registry.

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.

Study sites(170)

  • Children's Hospital of Alabama

    Birmingham, Alabama, United States

    Suspended

  • 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

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, United States

    Suspended

  • Arkansas Children's Hospital

    Little Rock, Arkansas, United States

    Recruiting

  • Kaiser Permanente Downey Medical Center

    Downey, California, United States

    Recruiting

  • 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

  • Sacred Heart Hospital

    Pensacola, Florida, United States

    Suspended

  • 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

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, United States

    Recruiting

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, United States

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, United States

    Recruiting

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, United States

    Recruiting

  • Children's Hospital of Michigan

    Detroit, Michigan, United States

    Recruiting

  • Michigan State University

    East Lansing, Michigan, United States

    Active, not recruiting

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, United States

    Recruiting

Showing 60 of 170 sites — filter to narrow it down. 160 of the 170 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.

Source: ClinicalTrials.gov record NCT04684368. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.

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