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NCT04684368 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
RECRUITING
Registry last update
2026-08-25

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.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
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. 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 ) * 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) * Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated. If a patient undergoes surgery and lumbar CSF cytology cannot be obtained at the time of surgery, then it should be performed at least 10 days following surgery and prior to study enrollment. False positive cytology can occur within 10 days of surgery * 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/gender 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
healthy Volunteers
false
maximum Age
29 Years
minimum Age
3 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Outline in Detailed Description.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Drug: Carboplatin
    3. Drug: Etoposide
    4. Biological: Filgrastim
    5. Drug: Ifosfamide
    6. Procedure: Magnetic Resonance Imaging
    7. Drug: Mesna
    8. Biological: Pegfilgrastim
    9. Other: Questionnaire Administration
    10. Radiation: Radiation Therapy
    11. Procedure: Second-Look Surgery
    label
    Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    type
    EXPERIMENTAL
  2. description
    See Outline in Detailed Description.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Drug: Carboplatin
    3. Drug: Etoposide
    4. Biological: Filgrastim
    5. Drug: Ifosfamide
    6. Procedure: Magnetic Resonance Imaging
    7. Drug: Mesna
    8. Biological: Pegfilgrastim
    9. Procedure: Peripheral Blood Stem Cell Transplantation
    10. Other: Questionnaire Administration
    11. Radiation: Radiation Therapy
    12. Procedure: Second-Look Surgery
    label
    Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Undergo collection of CSF and blood samples
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Specimen Collection
    type
    PROCEDURE
  2. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given IV
    name
    Carboplatin
    other Names
    1. Blastocarb
    2. Carboplat
    3. Carboplatin Hexal
    4. Carboplatino
    5. Carboplatinum
    6. Carbosin
    7. Carbosol
    8. Carbotec
    9. CBDCA
    10. Displata
    11. Ercar
    12. JM-8
    type
    DRUG
  3. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given IV
    name
    Etoposide
    other Names
    1. Demethyl Epipodophyllotoxin Ethylidine Glucoside
    2. EPEG
    3. Lastet
    4. Toposar
    5. Vepesid
    6. VP 16
    7. VP 16-213
    8. VP 16213
    9. VP-16
    10. VP-16-213
    11. VP-16213
    12. VP16
    type
    DRUG
  4. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given subcutaneously (SC) or IV
    name
    Filgrastim
    other Names
    1. Filgrastim Biosimilar Filgrastim-sndz
    2. Filgrastim Biosimilar Tbo-filgrastim
    3. Filgrastim XM02
    4. Filgrastim-aafi
    5. Filgrastim-ayow
    6. Filgrastim-sndz
    7. G-CSF
    8. Granix
    9. Neupogen
    10. Neutroval
    11. Nivestim
    12. Nivestym
    type
    BIOLOGICAL
  5. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given IV
    name
    Ifosfamide
    other Names
    1. Asta Z 4942
    2. Asta Z-4942
    3. Cyfos
    4. Holoxan
    5. Holoxane
    6. Ifex
    7. IFO
    8. IFO-Cell
    9. Ifolem
    10. Ifomida
    11. Ifomide
    12. Ifosfamidum
    type
    DRUG
  6. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Undergo MRI
    name
    Magnetic Resonance Imaging
    other Names
    1. Magnetic Resonance
    2. Magnetic Resonance Imaging (MRI)
    3. Magnetic resonance imaging (procedure)
    4. Magnetic Resonance Imaging Scan
    5. Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    6. MR
    7. MR Imaging
    8. MRI
    9. MRI Scan
    10. MRIs
    11. NMR Imaging
    12. NMRI
    type
    PROCEDURE
  7. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given IV or orally
    name
    Mesna
    other Names
    1. 2-Mercaptoethanesulfonate, Sodium Salt
    2. Ausobronc
    3. D-7093
    4. Filesna
    5. Mercaptoethane Sulfonate
    6. Mercaptoethanesulfonate
    7. Mesnex
    8. Mesnil
    9. Mesnum
    10. Mexan
    11. Mistabron
    12. Mistabronco
    type
    DRUG
  8. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Given SC
    name
    Pegfilgrastim
    other Names
    1. Dulastin
    2. Filgrastim SD-01
    3. filgrastim-SD/01
    4. Fulphila
    5. Fylnetra
    6. G-Lasta
    7. HSP-130
    8. Jinyouli
    9. Neulasta
    10. Neulastim
    11. Neupopeg
    12. Nyvepria
    type
    BIOLOGICAL
  9. arm Group Labels
    1. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Undergo PBSC transplant
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. PBSCT
    3. Peripheral Blood
    4. Peripheral Blood Progenitor Cell Transplantation
    5. PERIPHERAL BLOOD STEM CELL TRANSPLANT
    6. Peripheral Stem Cell Support
    7. Peripheral Stem Cell Transplant
    8. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
  10. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    2. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Ancillary studies
    name
    Questionnaire Administration
    type
    OTHER
  11. arm Group Labels
    1. Plan A (chemotherapy, WVSCI, second-look surgery if needed)
    description
    Undergo WVSCI radiation therapy
    name
    Radiation Therapy
    other Names
    1. Cancer Radiotherapy
    2. Energy Type
    3. ENERGY_TYPE
    4. Irradiate
    5. Irradiated
    6. Irradiation
    7. Radiation
    8. Radiation Therapy, NOS
    9. Radiotherapeutics
    10. Radiotherapy
    11. RT
    12. Therapy, Radiation
    type
    RADIATION
  12. arm Group Labels
    1. Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
    description
    Undergo radiation therapy
    name
    Radiation Therapy
    other Names
    1. Cancer Radiotherapy
    2. Energy Type
    3. ENERGY_TYPE
    4. Irradiate
    5. Irradiated
    6. Irradiation
    7. Radiation
    8. Radiation Therapy, NOS
    9. Radiotherapeutics
    10. Radiotherapy
    11. RT
    12. Therapy, Radiation
    type
    RADIATION
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
160
type
ESTIMATED
Registered outcome plans (not posted results)
other Outcomes
  1. description
    Will be assessed by the Wechsler Preschool and Primary Scale of Intelligence 4th Edition (WPPSI-IV), Wechsler Intelligence Scale for Children 5th Edition (WISC-V), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), depending on patient's age. One-sample confidence intervals will be used to estimate mean pairwise changes in intelligence scores between 2 time points within each treatment arm.
    measure
    Change in intelligence scores within each treatment arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  2. description
    Will be assessed by the Wechsler Preschool and Primary Scale of Intelligence 4th Edition (WPPSI- IV), Wechsler Intelligence Scale for Children 5th Edition (WISC V), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV), depending on patient's age. A 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.
    measure
    Change in intelligence scores between treatment arms
    time Frame
    Baseline up to 60 months post-treatment initiation
  3. description
    Will be assessed by the WISC-V or WAIS-IV processing speed index tasks. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within each treatment arm.
    measure
    Change in processing speed/attention within each treatment arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  4. description
    Will be assessed by the WISC-V or WAIS-IV processing speed index tasks. A 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.
    measure
    Change in processing speed/attention between the two treatment arms
    time Frame
    Baseline up to 60 months post-treatment initiation
  5. description
    Will be assessed by the Children's Memory Scale and California Verbal Learning Test. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.
    measure
    Change in immediate visual memory within each arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  6. description
    Will be assessed by the Behavior Assessment System for Children - 3rd Edition. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.
    measure
    Change in social-emotional functioning within each arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  7. description
    Will be assessed by the Adaptive Behavior Assessment System - 3rd Edition. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.
    measure
    Change in adaptive functioning within each arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  8. description
    Will be assessed by the Pediatric Quality of Life Inventory version 4.0. One-sample confidence intervals will be used to estimate mean pairwise changes in scores between 2 time points within treatment arms, as appropriate.
    measure
    Change in health-related quality of life within each arm
    time Frame
    Baseline up to 60 months post-treatment initiation
  9. description
    Will be assessed by the Pediatric Quality of Life Inventory version 4.0. 2-sample confidence interval approach will be used to estimate the difference in score changes between the two cohorts (WVSCI versus HDCSCR) in order to describe differential effects of the 2 treatment strategies.
    measure
    Change in health-related quality of life between the two treatment arms
    time Frame
    Baseline up to 60 months post-treatment initiation
  10. description
    Will summarize and compare functional outcomes, including cognitive, social and behavioral functioning, and auditory and neuro-endocrine function, in the context of the radiation therapy modality used. Two sample t-tests for specified timepoints within each of the two treatment cohorts (WVSCI versus HDCSCR) will be used for comparisons.
    measure
    Radiation modality (proton versus photon)
    time Frame
    Up to 10 years
  11. description
    Will compare early and late outcomes for proton and photon therapy with and without vertebral body sparing. Height and weight of subjects who are \< 13 years at the time of radiation therapy will be collected until subjects go off study or reach the age of 21, whichever is earlier. Percentile values standardizing height and weight based on appropriate growth curves will be used to compare cohorts treated with proton- versus photon-based radiation therapy.
    measure
    Growth comparisons following radiation by radiation modality
    time Frame
    Up to 10 years
  12. description
    Complete blood count values during radiation therapy will be used to compare these outcomes in the context of proton- versus photon-based radiation therapy.
    measure
    Complete blood count values following radiation by radiation modality
    time Frame
    Up to 1 year post treatment initiation
primary Outcomes
  1. description
    Will be measured by the number of progressions or deaths within 2 years of enrollment for the cohort treated with whole ventricular + spinal canal irradiation (WVSCI). The final analysis will include an exact binomial confidence interval of the failure rate for each of the failure types (local, distant/spinal or both) without adjustment for multiplicity.
    measure
    Failure rate
    time Frame
    Within 2 years of enrollment
  2. description
    Will be measured by the number of spinal relapses (spine alone or distant relapses including the spine) within 2 years of enrollment in patients treated with WVSCI. The final analysis will include an exact binomial confidence interval of spinal failure rate.
    measure
    Spinal failure rate
    time Frame
    Within 2 years of enrollment
secondary Outcomes
  1. description
    Will be assessed in patients treated with induction chemotherapy. Will be estimated using an exact binomial approach and its confidence interval.
    measure
    Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery
    time Frame
    Approximately 6 to 9 months post-treatment initiation
  2. description
    Will be assessed in patients treated with HDCSCR. Will be estimated using an exact binomial approach and its confidence interval.
    measure
    Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)
    time Frame
    Up to 2 years post-treatment initiation
  3. description
    Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based PFS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the primary analyses.
    measure
    Progression-free survival (PFS)
    time Frame
    From enrollment until disease progression or death from any cause for patients with events, and until final follow up for those who are event free at the time of analysis, assessed up to 10 years
  4. description
    Will be estimated separately for those treated with WVSCI and with HDCSCR + radiation therapy. Kaplan-Maier based OS curve estimates will be included, where patients who are lost to follow up will be treated as censored observations as part of the secondary analyses.
    measure
    Overall survival (OS)
    time Frame
    From enrollment until death from any cause for patients with events and until final follow up for those who are alive at the time of analysis, assessed up to 10 years
  5. description
    Will be analyzed in an exploratory manner with respect to radiation dose distribution.
    measure
    Patterns of disease recurrence/failure
    time Frame
    Up to 10 years
Full study description
brief Summary
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.
detailed Description
PRIMARY OBJECTIVES: I. To monitor outcome to ensure that children and young adults with localized central nervous system (CNS) non-germinomatous germ cell tumors (NGGCT) treated with induction chemotherapy followed by response evaluation and whole ventricular + spinal canal irradiation (WVSCI) will maintain the excellent 2-year progression free survival (PFS) rate as compared to ACNS0122 (NCT00047320). II. To improve disease control by decreasing the number of spinal relapses for patients who achieve a complete response (CR) or partial response (PR) and receive WVSCI as compared to whole ventricular radiation on ACNS1123 (NCT01602666). SECONDARY OBJECTIVES: I. To estimate the response rates to induction chemotherapy and WVSCI for localized NGGCT patients who achieve a CR/PR. II. To estimate the PFS and overall survival (OS) for localized NGGCT patients who achieve a CR/PR and receive WVSCI. III. To estimate the PFS and OS for patients with less than a CR/PR following Induction who subsequently receive high-dose chemotherapy with peripheral stem cell rescue (HDCSCR). IV. To estimate the response rate for patients with less than a CR/PR following Induction who subsequently receive HDCSCR. EXPLORATORY OBJECTIVES: I. To prospectively compare outcomes based on radiation modality, photon versus proton, including cognitive, social and behavioral functioning, auditory, and neuro-endocrine function. II. To compare spinal column growth and cell counts following radiation as measured by height and weight, and complete blood count (CBC) values during and after radiation therapy, based on treatment modality (photon versus \[vs.\] proton therapy) and planned inclusion/exclusion of the vertebral body in patients \< 13 years of age. III. To compare local vs. central review recommendations for second-look surgery and document barriers for performing such surgeries as well as their clinical benefit in pediatric NGGCT. IV. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults with localized CNS NGGCT with testing as per the Children's Oncology Group (COG) Standardized Neuropsychological and Behavioral Battery. V. To evaluate patterns of disease recurrence/failure with respect to radiation dose distribution. OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 of cycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation \[WVSCI\] or high-dose chemotherapy with peripheral stem cell rescue \[HDCSCR\]) based on response to induction chemotherapy: * Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR. * Patients who achieve less than radiographic CR/PR with marker normalization proceed to second-look surgery (unless contraindicated). If second-look surgery reveals mature teratoma or non-viable tumor, proceed to WVSCI. If second-look surgery reveals viable tumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery are removed from protocol therapy but remain on study for follow-up. * Patients who achieve less than radiographic CR/PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed. * Patients who achieve radiographic PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed. PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-look surgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity. PLAN B (CONSOLIDATION THERAPY \[HDCSCR\]): Within 6-8 weeks of the end of induction chemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI), as well as collection of cerebral spinal fluid (CSF) and blood sample throughout the trial. After completion of study treatment, patients are followed for up to 10 years.
Source references
Source notices and limitations
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      occurrences
      1. context exact
        /or institutional clinical trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1839"><li><strong><a href="/clinicaltrials/NCT04684368">ACNS2021 (NCT04684368)</a></strong> (A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT)<strong>:</strong> This phase II
        end
        104618
        exact text
        NCT04684368
        start
        104607
      2. context exact
        cal trial that is currently being conducted:</p> <div class="pdq-content-list"><ul id="_1839"><li><strong><a href="/clinicaltrials/NCT04684368">ACNS2021 (NCT04684368)</a></strong> (A Study of a New Way to Treat Children and Young Adults With a Brain Tumor Called NGGCT)<strong>:</strong> This phase II trial studies the effec
        end
        104641
        exact text
        NCT04684368
        start
        104630
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      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/4e7a33a8cfb84ff4e4.html
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      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:32.688337+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      8320ccfb31415815eab14c8336092aa4b9bb6a5abe4c47bef9b6fec1cb75f8eb
      source title
      Childhood Central Nervous System Germ Cell Tumors Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: October 8, 2024
        datetime
        2024-10-08T12:00:00Z
        display
        October 8, 2024

    Preserved source evidence · Not medical advice