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RecruitingNCT04684368Updated Sep 23, 2026

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

A Phase 2 interventional study of Biospecimen Collection and Carboplatin in Central Nervous System Nongerminomatous Germ Cell Tumor, Choriocarcinoma and Embryonal Carcinoma, sponsored by Children's Oncology Group. Recruiting at 170 sites in 4 countries. Open to participants aged 3 Years to 29 Years. Per ClinicalTrials.gov, last updated 2026-09-23.

Sponsored by Children's Oncology Group · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
160
Allocation
Non-randomized
Ages
3 Years to 29 Years
Sex
All
01

Study 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.

Read the 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 6-9 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
3 Years to 29 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
160 participants (estimated)

Study arms

  • Experimental
    Plan A (chemotherapy, WVSCI, second-look surgery if needed)

    See Outline in Detailed Description.

    Procedure: Biospecimen Collection · Drug: Carboplatin · Drug: Etoposide · Biological: Filgrastim · Drug: Ifosfamide · Procedure: Magnetic Resonance Imaging · Drug: Mesna · Biological: Pegfilgrastim · Other: Questionnaire Administration · Radiation: Radiation Therapy · Procedure: Second-Look Surgery

  • Experimental
    Plan B (chemotherapy, HDCSCR, second-look surgery if needed)

    See Outline in Detailed Description.

    Procedure: Biospecimen Collection · Drug: Carboplatin · Drug: Etoposide · Biological: Filgrastim · Drug: Ifosfamide · Procedure: Magnetic Resonance Imaging · Drug: Mesna · Biological: Pegfilgrastim · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Questionnaire Administration · Radiation: Radiation Therapy · Procedure: Second-Look Surgery · Drug: Thiotepa

Interventions

  • ProcedureBiospecimen Collection

    Undergo collection of CSF and blood samples

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • DrugCarboplatin

    Given IV

    Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

  • DrugEtoposide

    Given IV

    Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP-16213, VP16, VP16213

  • BiologicalFilgrastim

    Given subcutaneously (SC) or IV

    Also known as: Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi, Filgrastim-ayow, Filgrastim-sndz, G-CSF, Granix, Neupogen, Neutroval, Nivestim, Nivestym, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, Releuko, rG-CSF, Tbo-filgrastim, Tevagrastim, XM02, Zarxio

  • DrugIfosfamide

    Given IV

    Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • DrugMesna

    Given IV or orally

    Also known as: 2-Mercaptoethanesulfonate, Sodium Salt, Ausobronc, D-7093, Filesna, Mercaptoethane Sulfonate, Mercaptoethanesulfonate, Mesnex, Mesnil, Mesnum, Mexan, Mistabron, Mistabronco, Mitexan, Mucofluid, Mucolene, UCB 3983, Uromitexan, Ziken

  • BiologicalPegfilgrastim

    Given SC

    Also known as: Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01, filgrastim-SD/01, Fulphila, Fylnetra, G-Lasta, Grasustek, HSP-130, Jinyouli, Neulasta, Neulastim, Neupopeg, Nyvepria, PEG-filgrastim, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar PF-06881894, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, Pegfilgrastim-apgf, Pegfilgrastim-bmez, Pegfilgrastim-cbqv, Pegfilgrastim-cegf, Pegfilgrastim-dyru, Pegfilgrastim-fpgk, Pegfilgrastim-gras, Pegfilgrastim-jmdb, Pegfilgrastim-pbbk, Pegfilgrastim-pelg, Pegfilgrastim-pelm, Pegylated G-CSF, Pegylated GCSF, Pegylated Granulocyte Colony Stimulating Factor, Pelgraz, Pelmeg, PF-06881894, SD-01, SD-01 sustained duration G-CSF, Stimufend, Tripegfilgrastim, Udenyca, Ziextenzo

  • ProcedurePeripheral Blood Stem Cell Transplantation

    Undergo PBSC transplant

    Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

  • OtherQuestionnaire Administration

    Ancillary studies

  • RadiationRadiation Therapy

    Undergo WVSCI radiation therapy

    Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

  • RadiationRadiation Therapy

    Undergo Craniospinal radiation therapy

    Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

  • ProcedureSecond-Look Surgery

    Undergo second-look surgery if needed

    Also known as: Reoperation, Repeat Surgery, Second Look, Surgical Revision

  • DrugThiotepa

    Given IV

    Also known as: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa, SH 105, SH-105, SH105, STEPA, Tepadina, Tepylute, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

05

What researchers measure

Primary outcomes

  1. Failure rate

    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.

    Time frame: Within 2 years of enrollment

  2. Spinal failure rate

    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.

    Time frame: Within 2 years of enrollment

Secondary outcomes

  1. Radiographic complete response (CR)/partial response (PR) with marker normalization rate post induction/second-look surgery

    Will be assessed in patients treated with induction chemotherapy. Will be estimated using an exact binomial approach and its confidence interval.

    Time frame: Approximately 6 to 9 months post-treatment initiation

  2. Radiographic complete response (CR)/partial response (PR) with marker normalization rate post high-dose chemotherapy with peripheral stem cell rescue (HDCSCR)

    Will be assessed in patients treated with HDCSCR. Will be estimated using an exact binomial approach and its confidence interval.

    Time frame: Up to 2 years post-treatment initiation

  3. Progression-free survival (PFS)

    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.

    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. Overall survival (OS)

    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.

    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. Patterns of disease recurrence/failure

    Will be analyzed in an exploratory manner with respect to radiation dose distribution.

    Time frame: Up to 10 years

Other outcomes

  1. Change in intelligence scores within each treatment arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  2. Change in intelligence scores between treatment arms

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  3. Change in processing speed/attention within each treatment arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  4. Change in processing speed/attention between the two treatment arms

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  5. Change in immediate visual memory within each arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  6. Change in social-emotional functioning within each arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  7. Change in adaptive functioning within each arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  8. Change in health-related quality of life within each arm

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  9. Change in health-related quality of life between the two treatment arms

    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.

    Time frame: Baseline up to 60 months post-treatment initiation

  10. Radiation modality (proton versus photon)

    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.

    Time frame: Up to 10 years

  11. Growth comparisons following radiation by radiation modality

    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.

    Time frame: Up to 10 years

  12. Complete blood count values following radiation by radiation modality

    Complete blood count values during radiation therapy will be used to compare these outcomes in the context of proton- versus photon-based radiation therapy.

    Time frame: Up to 1 year post treatment initiation

  13. Local versus central review recommendations for second-look surgery

    Will summarize the local versus central review recommendations for second-look surgery and document any discrepancies.

    Time frame: Up to 1 year post treatment initiation

06

Study locations

160 of 170 sites recruiting
  • Children's Hospital of Alabama
    Birmingham, Alabama 35233, United States
    Suspended
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
    Recruiting
  • Banner Children's at Desert
    Mesa, Arizona 85202, United States
    • Site Public Contact · Contact · 480-412-3100
    • Joseph C. Torkildson · Principal investigator
    Recruiting
  • Phoenix Childrens Hospital
    Phoenix, Arizona 85016, United States
    • Site Public Contact · Contact · 602-546-0920
    • Michael R. Mangum · Principal investigator
    Recruiting
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona 85719, United States
    Suspended
  • Arkansas Children's Hospital
    Little Rock, Arkansas 72202-3591, United States
    • Site Public Contact · Contact · 501-364-7373
    • Michael W. Bishop · Principal investigator
    Recruiting
  • Kaiser Permanente Downey Medical Center
    Downey, California 90242, United States
    • Site Public Contact · Contact · 626-564-3455
    • Hung N. Tran · Principal investigator
    Recruiting
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
    • Site Public Contact · Contact · 909-558-4050
    • Albert Kheradpour · Principal investigator
    Recruiting
  • Miller Children's and Women's Hospital Long Beach
    Long Beach, California 90806, United States
    • Site Public Contact · Contact · 562-933-5600
    • Jacqueline N. Casillas · Principal investigator
    Recruiting
  • Children's Hospital Los Angeles
    Los Angeles, California 90027, United States
    • Site Public Contact · Contact · 323-361-4110
    • Tom B. Davidson · Principal investigator
    Recruiting
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
    • Site Public Contact · Contact · clinical.trials@kp.org · 800-398-3996
    • Hung N. Tran · Principal investigator
    Recruiting
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
    Recruiting
  • Valley Children's Hospital
    Madera, California 93636, United States
    Recruiting
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
    • Site Public Contact · Contact · Kpoct@kp.org · 877-642-4691
    • Aarati V. Rao · Principal investigator
    Recruiting
  • Children's Hospital of Orange County
    Orange, California 92868, United States
    • Site Public Contact · Contact · oncresearch@choc.org · 714-509-8646
    • Elyssa M. Rubin · Principal investigator
    Recruiting
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto, California 94304, United States
    • Site Public Contact · Contact · ccto-office@stanford.edu · 800-694-0012
    • Jay Michael S. Balagtas · Principal investigator
    Recruiting
  • Rady Children's Hospital - San Diego
    San Diego, California 92123, United States
    • Site Public Contact · Contact · 858-966-5934
    • William D. Roberts · Principal investigator
    Recruiting
  • UCSF Medical Center-Mission Bay
    San Francisco, California 94158, United States
    • Site Public Contact · Contact · cancertrials@ucsf.edu · 877-827-3222
    • Alyssa T. Reddy · Principal investigator
    Recruiting
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
    Recruiting
  • Connecticut Children's Medical Center
    Hartford, Connecticut 06106, United States
    • Site Public Contact · Contact · 860-545-9981
    • Michael S. Isakoff · Principal investigator
    Recruiting
  • Smilow Cancer Center/Yale-New Haven Hospital
    New Haven, Connecticut 06510, United States
    • Site Public Contact · Contact · canceranswers@yale.edu · 203-785-5702
    • Asher M. Marks · Principal investigator
    Recruiting
  • Yale University
    New Haven, Connecticut 06520, United States
    • Site Public Contact · Contact · canceranswers@yale.edu · 203-785-5702
    • Asher M. Marks · Principal investigator
    Recruiting
  • Alfred I duPont Hospital for Children
    Wilmington, Delaware 19803, United States
    Recruiting
  • Children's National Medical Center
    Washington D.C., District of Columbia 20010, United States
    Recruiting
  • Golisano Children's Hospital of Southwest Florida
    Fort Myers, Florida 33908, United States
    Recruiting
  • UF Health Cancer Institute - Gainesville
    Gainesville, Florida 32610, United States
    • Site Public Contact · Contact · cancer-center@ufl.edu · 352-273-8010
    • Brian Stover · Principal investigator
    Recruiting
  • Nemours Children's Clinic-Jacksonville
    Jacksonville, Florida 32207, United States
    Recruiting
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
    • Site Public Contact · Contact · 305-243-2647
    • Bradley Gampel · Principal investigator
    Recruiting
  • Nicklaus Children's Hospital
    Miami, Florida 33155, United States
    • Site Public Contact · Contact · 888-624-2778
    • Ziad A. Khatib · Principal investigator
    Recruiting
  • Arnold Palmer Hospital for Children
    Orlando, Florida 32806, United States
    Recruiting
  • Nemours Children's Hospital
    Orlando, Florida 32827, United States
    Recruiting
  • Nemours Children's Clinic - Pensacola
    Pensacola, Florida 32504, United States
    Recruiting
  • Sacred Heart Hospital
    Pensacola, Florida 32504, United States
    Suspended
  • Johns Hopkins All Children's Hospital
    St. Petersburg, Florida 33701, United States
    • Site Public Contact · Contact · Ashley.Repp@jhmi.edu · 727-767-4784
    • Stacie L. Stapleton · Principal investigator
    Recruiting
  • Saint Joseph's Hospital/Children's Hospital-Tampa
    Tampa, Florida 33607, United States
    Recruiting
  • Children's Healthcare of Atlanta - Arthur M Blank Hospital
    Atlanta, Georgia 30329, United States
    • Site Public Contact · Contact · Olivia.Floyd@choa.org · 404-785-0232
    • Jason R. Fangusaro · Principal investigator
    Recruiting
  • Kapiolani Medical Center for Women and Children
    Honolulu, Hawaii 96826, United States
    • Site Public Contact · Contact · 808-983-6090
    • Wade T. Kyono · Principal investigator
    Recruiting
  • Saint Luke's Cancer Institute - Boise
    Boise, Idaho 83712, United States
    • Site Public Contact · Contact · eslinget@slhs.org · 208-381-2774
    • Martha M. Pacheco · Principal investigator
    Recruiting
  • Lurie Children's Hospital-Chicago
    Chicago, Illinois 60611, United States
    • Site Public Contact · Contact · 773-880-4562
    • Alicia Lenzen · Principal investigator
    Recruiting
  • University of Illinois
    Chicago, Illinois 60612, United States
    • Site Public Contact · Contact · 312-355-3046
    • Dipti S. Dighe · Principal investigator
    Recruiting
  • University of Chicago Comprehensive Cancer Center
    Chicago, Illinois 60637, United States
    Recruiting
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
    • Site Public Contact · Contact · 708-226-4357
    • Eugene Suh · Principal investigator
    Recruiting
  • OSF Children's Hospital of Illinois
    Peoria, Illinois 61637, United States
    Recruiting
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
    • Sandeep Batra · Contact · batras@iu.edu · 317-944-8784
    • Sandeep Batra · Principal investigator
    Recruiting
  • Blank Children's Hospital
    Des Moines, Iowa 50309, United States
    Recruiting
  • University of Iowa/Holden Comprehensive Cancer Center
    Iowa City, Iowa 52242, United States
    • Site Public Contact · Contact · 800-237-1225
    • Andrew P. Groves · Principal investigator
    Recruiting
  • University of Kentucky/Markey Cancer Center
    Lexington, Kentucky 40536, United States
    • Site Public Contact · Contact · 859-257-3379
    • James T. Badgett · Principal investigator
    Recruiting
  • Norton Children's Hospital
    Louisville, Kentucky 40202, United States
    Recruiting
  • Ochsner Medical Center Jefferson
    New Orleans, Louisiana 70121, United States
    Recruiting
  • Eastern Maine Medical Center
    Bangor, Maine 04401, United States
    • Site Public Contact · Contact · 207-973-4274
    • Daniel L. Callaway · Principal investigator
    Recruiting
  • Maine Children's Cancer Program
    Scarborough, Maine 04074, United States
    Recruiting
  • Sinai Hospital of Baltimore
    Baltimore, Maryland 21215, United States
    • Site Public Contact · Contact · 410-601-9083
    • Jason M. Fixler · Principal investigator
    Recruiting
  • Johns Hopkins University/Sidney Kimmel Cancer Center
    Baltimore, Maryland 21287, United States
    • Site Public Contact · Contact · jhcccro@jhmi.edu · 410-955-8804
    • Kenneth J. Cohen · Principal investigator
    Recruiting
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts 02114, United States
    • Site Public Contact · Contact · 877-726-5130
    • Laura Wiltsie · Principal investigator
    Recruiting
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    • Site Public Contact · Contact · 877-442-3324
    • Kee Kiat Yeo · Principal investigator
    Recruiting
  • C S Mott Children's Hospital
    Ann Arbor, Michigan 48109, United States
    • Site Public Contact · Contact · 800-865-1125
    • Andrea T. Franson · Principal investigator
    Recruiting
  • Children's Hospital of Michigan
    Detroit, Michigan 48201, United States
    Recruiting
  • Michigan State University
    East Lansing, Michigan 48823, United States
    Active, not recruiting
  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    Grand Rapids, Michigan 49503, United States
    Recruiting
  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
    Grand Rapids, Michigan 49503, United States
    Recruiting
  • Corewell Health Children's
    Royal Oak, Michigan 48073, United States
    • Site Public Contact · Contact · 248-551-7695
    • Marie V. Nelson · Principal investigator
    Recruiting
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
    Minneapolis, Minnesota 55404, United States
    Recruiting
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
    • Site Public Contact · Contact · 855-776-0015
    • Joseph Z. Wilson · Principal investigator
    Recruiting
  • University of Mississippi Medical Center
    Jackson, Mississippi 39216, United States
    • Site Public Contact · Contact · 601-815-6700
    • Amanda Strobel · Principal investigator
    Recruiting
  • University of Missouri Children's Hospital
    Columbia, Missouri 65212, United States
    Recruiting
  • Children's Mercy Hospitals and Clinics
    Kansas City, Missouri 64108, United States
    Recruiting
  • Cardinal Glennon Children's Medical Center
    St Louis, Missouri 63104, United States
    • Site Public Contact · Contact · 314-268-4000
    • William S. Ferguson · Principal investigator
    Recruiting
  • Washington University School of Medicine
    St Louis, Missouri 63110, United States
    • Site Public Contact · Contact · info@siteman.wustl.edu · 800-600-3606
    • Mohamed S. Abdelbaki · Principal investigator
    Recruiting
  • Mercy Hospital Saint Louis
    St Louis, Missouri 63141, United States
    • Site Public Contact · Contact · 314-251-7066
    • Robin D. Hanson · Principal investigator
    Recruiting
  • Children's Hospital and Medical Center of Omaha
    Omaha, Nebraska 68114, United States
    • Site Public Contact · Contact · 402-955-3949
    • Jill C. Beck · Principal investigator
    Recruiting
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
    • Site Public Contact · Contact · unmcrsa@unmc.edu · 402-559-6941
    • Jill C. Beck · Principal investigator
    Recruiting
  • Oncology Las Vegas - Henderson
    Henderson, Nevada 89074, United States
    Suspended
  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    Las Vegas, Nevada 89135, United States
    Suspended
  • Renown Regional Medical Center
    Reno, Nevada 89502, United States
    • Site Public Contact · Contact · Renown-CRD@renown.org · 775-982-5050
    • Alan K. Ikeda · Principal investigator
    Recruiting
  • Cancer Care Specialists - Reno
    Reno, Nevada 89511, United States
    Suspended
  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
    Lebanon, New Hampshire 03756, United States
    Recruiting
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
    • Site Public Contact · Contact · 551-996-2897
    • Derek R. Hanson · Principal investigator
    Recruiting
  • Morristown Medical Center
    Morristown, New Jersey 07960, United States
    • Site Public Contact · Contact · 973-971-5900
    • Kathryn L. Laurie · Principal investigator
    Recruiting
  • Saint Peter's University Hospital
    New Brunswick, New Jersey 08901, United States
    Recruiting
  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
    New Brunswick, New Jersey 08903, United States
    • Site Public Contact · Contact · 732-235-8675
    • Nehal S. Parikh · Principal investigator
    Recruiting
  • Newark Beth Israel Medical Center
    Newark, New Jersey 07112, United States
    Recruiting
  • Saint Joseph's Regional Medical Center
    Paterson, New Jersey 07503, United States
    • Site Public Contact · Contact · HallL@sjhmc.org · 973-754-2207
    • Alissa Kahn · Principal investigator
    Recruiting
  • Albany Medical Center
    Albany, New York 12208, United States
    • Site Public Contact · Contact · 518-262-5513
    • Lauren R. Weintraub · Principal investigator
    Recruiting
  • Maimonides Medical Center
    Brooklyn, New York 11219, United States
    • Site Public Contact · Contact · 718-765-2500
    • Mahmut Y. Celiker · Principal investigator
    Recruiting
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
    Recruiting
  • The Steven and Alexandra Cohen Children's Medical Center of New York
    New Hyde Park, New York 11040, United States
    • Site Public Contact · Contact · 718-470-3460
    • Mark P. Atlas · Principal investigator
    Recruiting
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    New York, New York 10016, United States
    Recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
    • Site Public Contact · Contact · 212-639-7592
    • Sameer Farouk Sait · Principal investigator
    Recruiting
  • University of Rochester
    Rochester, New York 14642, United States
    • Site Public Contact · Contact · 585-275-5830
    • David N. Korones · Principal investigator
    Recruiting
  • Stony Brook University Medical Center
    Stony Brook, New York 11794, United States
    • Site Public Contact · Contact · 800-862-2215
    • Laura E. Hogan · Principal investigator
    Recruiting
  • State University of New York Upstate Medical University
    Syracuse, New York 13210, United States
    • Site Public Contact · Contact · 315-464-5476
    • Melanie A. Comito · Principal investigator
    Recruiting
  • Montefiore Medical Center-Einstein Campus
    The Bronx, New York 10461, United States
    • Site Public Contact · Contact · eskwak@montefiore.org · 718-379-6866
    • Alice Lee · Principal investigator
    Recruiting
  • Montefiore Medical Center - Moses Campus
    The Bronx, New York 10467, United States
    • Site Public Contact · Contact · eskwak@montefiore.org · 718-379-6866
    • Alice Lee · Principal investigator
    Recruiting
  • New York Medical College
    Valhalla, New York 10595, United States
    • Site Public Contact · Contact · 914-594-3794
    • Andrew J. Bellantoni · Principal investigator
    Recruiting
  • Carolinas Medical Center/Levine Cancer Institute
    Charlotte, North Carolina 28203, United States
    • Site Public Contact · Contact · 800-804-9376
    • Joel A. Kaplan · Principal investigator
    Recruiting
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
    • Site Public Contact · Contact · 888-275-3853
    • Jessica M. Sun · Principal investigator
    Recruiting
  • East Carolina University
    Greenville, North Carolina 27834, United States
    • Site Public Contact · Contact · eubankss@ecu.edu · 252-744-1015
    • Andrea R. Whitfield · Principal investigator
    Recruiting
  • Wake Forest University Health Sciences
    Winston-Salem, North Carolina 27157, United States
    • Site Public Contact · Contact · 336-713-6771
    • Sarah Supples · Principal investigator
    Recruiting
  • Sanford Broadway Medical Center
    Fargo, North Dakota 58122, United States
    Recruiting

Showing the first 100 of 170 sites across 4 countries.

07

Registry details

Key details

Study ID
NCT04684368
Lead sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Dec 24, 2020
Start date
Jul 13, 2021
Primary completion
Dec 21, 2029 (estimated)
Completion
Dec 21, 2029 (estimated)
Last update
Sep 23, 2026

Study contacts

Shannon M MacDonald
principal investigator · Children's Oncology Group

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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