Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma

NCT00602667 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: SJYC07R01CA154619NCI-2011-01193
• Study Type: interventional
• Target: 293
• Locations: 2 countries
• Sites: 6

Brief Summary

RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat brain tumors in young children. Using chemotherapy gives the brain more time to develop before radiation is given. The chemotherapy in this study includes the drug methotrexate. This drug was an important part of the two clinical trials which resulted in the best survival results for children less than 3 years of age with medulloblastoma. Most patients treated on this trial will also receive radiation which is carefully targeted to the area of the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system tumors.

Conditions

Brain and Central Nervous System Tumors

Keywords

untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood pineoblastoma; childhood atypical teratoid/rhabdoid tumor; childhood choroid plexus tumor; childhood high grade glioma; newly diagnosed childhood ependymoma

Outcome Measures

Primary Outcomes (3)

• Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients

  Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.

  From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment

• Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup

  Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile.

  From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment

• Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients

  Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis.

  From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year after

Secondary Outcomes (79)

• Number of Participants With Chromosomal Abnormalities

  Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

• Numbers of Patients With Gene Alterations

  Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

• Numbers of Patients With Molecular Abnormalities by Tumor Type

  Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

• Number of Successful Collections for Frozen and Fixed Tumor Samples

  Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

• Event-free Survival (EFS) Compared to Historical Controls

  From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 years

Study Arms (3)

Low-Risk Patients

EXPERIMENTAL

Patients with GTR/M0 medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy. Note: Accrual to the low-risk medulloblastoma cohort is closed as of 12/2/2015. Accrual to the low-risk high grade glioma remains open.

Drug: Induction Chemotherapy; Drug: Low-Risk Therapy

High-Risk Patients

EXPERIMENTAL

Patients with CNS metastatic disease will receive induction chemotherapy and high-risk therapy.

Drug: Induction Chemotherapy; Drug: High-Risk Therapy

Intermediate-Risk Therapy

EXPERIMENTAL

Patients with M0 medulloblastoma or nodular desmoplastic histology with less than a GTR, other histologic diagnoses with no metastatic disease, will receive induction chemotherapy and intermediate-risk therapy.

Drug: Induction Chemotherapy; Drug: Intermediate-Risk Therapy

Interventions

Induction Chemotherapy DRUG

All patients will receive 4 identical cycles of induction chemotherapy including highdose (5 g/m2 or 2.5g/m2 for patients less than or equal to 31 days of age at enrollment) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide.

Also known as: MTX (methotrexate), Oncovin(R) (vincristine), Platinol-AQ(R) (cisplatin), Cytoxan(R) (cyclophosphamide)

High-Risk Patients; Intermediate-Risk Therapy; Low-Risk Patients

Low-Risk Therapy DRUG

Induction will be followed by further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).

Also known as: Cytoxan(R) (cyclophosphamide), Paraplatin(R) (carboplatin), Vepesid(R), VP-16 (etoposide), Hycamptin(R) (topotecan), Tarceva(TM) (erlotinib)

Low-Risk Patients

High-Risk Therapy DRUG

High risk patients will also receive vinblastine with each course of induction chemotherapy. Induction will be followed by either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).

Also known as: Velban(R) (vinblastine), Cytoxan(R) (cyclophosphamide), Hycamptin(R) (topotecan), Tarceva(TM) (erlotinib), Vepesid(R), VP-16 (etoposide)

High-Risk Patients

Intermediate-Risk Therapy DRUG

Induction will be followed by consolidation focal radiotherapy (RT) to the tumor bed. Patients less than 12 months old upon completion of induction will receive low risk chemotherapy to delay RT until the age of 12 months. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16). Note: The option to receive focal proton beam irradiation was suspended 10/29/2015. Focal photon beam irradiation continues as part of the treatment plan.

Also known as: Cytoxan(R) (cyclophosphamide), Hycamptin(R) (topotecan), Tarceva(TM) (erlotinib), Vepesid(R), VP-16 (etoposide)

Intermediate-Risk Therapy

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

Histologically confirmed newly diagnosed CNS tumors of any of the following : * Medulloblastoma (all histologic subtypes, including medullomyoblastoma and melanotic medulloblastoma) * Supratentorial primitive neuroectodermal tumor (PNET) (including CNS neuroblastoma or ganglioneuroblastoma, medulloepithelioma, and ependymoblastoma) * Pineoblastoma * Atypical teratoid rhabdoid tumor (ATRT) * Choroid plexus carcinoma * High grade glioma (including anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, pleomorphic xanthoastrocytoma with anaplastic features, high-grade astroblastoma , anaplastic pilocytic astrocytoma, malignant glioneuronal tumor, glioblastoma multiforme), or gliosarcoma, * Ependymoma (including all ependymoma histological variants) * Age \< 3 years at time of diagnosis for all histological diagnosis. Medulloblastoma patients ≥ 3 and \< 5years old at diagnosis who have non-metastatic disease with no more than 1cm2 of residual tumor are also eligible. * Meets criteria for 1 of the following risk groups: * Low-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma, including medulloblastoma with extensive nodularity * Focal areas of anaplasia or other atypical features suggesting more aggressive phenotype in a tumor otherwise considered nodular desmoplastic should be treated on the intermediate-risk group, with final risk stratification at the discretion of principal investigator and study pathologist * No evidence of CNS metastasis 7 to 28 days after surgery by MRI and cytologic examination of lumbar cerebrospinal fluid (CSF) * Ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1 disease when lumbar puncture is medically contraindicated * Intermediate-risk group assignment when there is no other evidence of metastasis and CSF sampling is not possible * Gross total resection, defined as residual tumor or imaging abnormality (not definitive for residual tumor) with a size of \< 1 cm2 confirmed on postoperative CT scan or MRI * Brain stem invasion by the tumor in the absence of imaging evidence of residual tumor (tumor size \< 1 cm2) and otherwise meets criteria for the low-risk group, the patient will be classified as low-risk * Desmoplastic medulloblastoma patients who are ≥3 -\<5 years of age will NOT be eligible for the low risk arm of the protocol. * Intermediate-risk group: * Histologically confirmed nodular desmoplastic medulloblastoma with less than gross total resection and no evidence of metastasis * Any eligible histologic diagnosis other than desmoplastic medulloblastoma with no evidence of CNS metastasis * Medulloblastoma patients who are ≥3 and \< 5 yrs of age irrespective of histology and with no evidence of CNS metastasis * High-risk group: * Any eligible histologic diagnosis with evidence of CNS metastasis * Patients with extraneural metastasis are eligible for treatment on the high-risk group PATIENT CHARACTERISTICS: * Lansky performance status ≥ 30 (except for posterior fossa syndrome) * WBC \> 2,000/mm3 * Platelets \> 50,000/mm3 (without support) * Hemoglobin \> 8 g/dL (with or without support) * ANC \> 500/mm3 * Serum creatinine \< 3 times upper limit of normal (ULN) * ALT \< 5 times ULN * Total bilirubin \< 3 times ULN PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No more than 31 days since prior definitive surgery * No prior radiotherapy or chemotherapy other than corticosteroid therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• University of Florida: collaborator
• National Cancer Institute (NCI): collaborator
• The Pew Charitable Trusts: collaborator

Study Sites (6)

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Children's Hospitals and Clinics of Minnesota - St. Paul

Saint Paul, Minnesota, 55102, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Lady Cilento Children's Hospital, Brisbane

Brisbane, Queensland, 4029, Australia

Location

Related Publications (3)

• Ali JS, Ashford JM, Swain MA, Harder LL, Carlson-Green BL, Miller JM, Wallace J, Kaner RJ, Billups CA, Onar-Thomas A, Merchant TE, Gajjar A, Conklin HM. Predictors of Cognitive Performance Among Infants Treated for Brain Tumors: Findings From a Multisite, Prospective, Longitudinal Trial. J Clin Oncol. 2021 Jul 20;39(21):2350-2358. doi: 10.1200/JCO.20.01687. Epub 2021 May 4.

  PMID: 33945291 DERIVED

• Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P Jr, Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V, Northcott PA. Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. J Clin Oncol. 2021 Mar 1;39(7):807-821. doi: 10.1200/JCO.20.01359. Epub 2021 Jan 27.

  PMID: 33502920 DERIVED

• Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, Bowers DC, Bendel A, Fisher PG, Partap S, Crawford JR, Hassall T, Indelicato DJ, Boop F, Klimo P, Sabin ND, Patay Z, Merchant TE, Stewart CF, Orr BA, Korbel JO, Jones DTW, Sharma T, Lichter P, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Sanders RP, Onar-Thomas A, Ellison DW, Gajjar A, Northcott PA. Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Lancet Oncol. 2018 Jun;19(6):768-784. doi: 10.1016/S1470-2045(18)30204-3. Epub 2018 May 16.

  PMID: 29778738 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Central Nervous System Neoplasms; Rhabdoid Tumor; Choroid Plexus Neoplasms

Interventions

Induction Chemotherapy; Methotrexate; Vincristine; Cisplatin; Cyclophosphamide; Carboplatin; Etoposide; Topotecan; Erlotinib Hydrochloride; Vinblastine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Cerebral Ventricle Neoplasms; Brain Neoplasms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Camptothecin; Quinazolines

Limitations and Caveats

Results for the some of the secondary objectives are not available yet. These results will be posted as they become available.

Results Point of Contact

• Title: Amar Gajjar, MD
• Organization: St. Jude Children's Research Hospital

amar.gajjar@stjude.org

866-278-5833

Study Officials

• Amar Gajjar, MD

  St. Jude Children's Research Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2008
• First Posted: January 28, 2008
• Study Start: December 17, 2007
• Primary Completion: September 27, 2017
• Study Completion: April 1, 2026
• Last Updated: January 13, 2026
• Results First Posted: January 30, 2019

Record last verified: 2026-01

Locations

US (5); AU (1)