SJYC07: Risk-Adapted Therapy in Treating Young Children with Brain Tumors

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

Category:

Brain Tumor

Diseases Treated:

ATRT, PNET, medulloblastoma and other embryonal brain tumors, high-grade glioma, choroid plexus carcinoma or ependymoma

Eligibility Overview:

  • Newly diagnosed brain tumor or tumor of the central nervous system and less than 3 years of age
  • Children between 3 and 5 years old with medulloblastoma  that has not spread  into the fluid that surrounds the brain and spinal cord can also be treated on this trial
  • No prior radiation therapy or chemotherapy
  1. Brief Summary

    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.

    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.

    Primary Objectives

    • To identify patterns of methylation profiling that are associated with progression-free survival among young pediatric patients with medulloblastoma treated with risk-adapted therapy
    • To estimate the event-free survival distribution of young medulloblastoma patients treated with risk-adapted therapy

    Trial Outline

    This is a multicenter study. Patients are stratified according to disease risk (low-risk vs. intermediate-risk vs. high-risk). Therapy consists of risk-adapted induction, consolidation and maintenance chemotherapy. Focal irradiation is given to intermediate risk patients who have reached at least 12 months of age upon completion of induction. Intermediate risk patients who have not will receive low-risk chemotherapy to delay RT until the age of 12 months.

    Interventions

    Drug: Induction chemotherapy

    All patients will receive 4 identical cycles of induction chemotherapy, including high-dose (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.

    Drug: Low-risk therapy

    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).

    Drug: High-risk therapy

    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).

    Drug: Intermediate-risk therapy

    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).

    Study Arms

    Experimental: Low-risk patients

    Patients with GTR/M0 medulloblastoma, nodular desmoplastic or high grade glioma histology will receive induction chemotherapy and low-risk therapy.

    Experimental: High-risk patients

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

    Experimental: Intermediate-risk therapy

    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.

    Eligibility Criteria

    • 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

    Study Design

    • Allocation: Non-randomized
    • Endpoint Classification: Safety/Efficacy study
    • Intervention Model: Parallel assignment
    • Masking: Open label
    • Primary Purpose: Treatment
  2. About this clinical trial

    SJYC07 is a clinical trial for young children with cancerous brain tumors. Fifty percent of brain tumors found in children less than 5 years old are either medulloblastoma or ependymal tumors

    • Medulloblastoma is a cancerous brain tumor that is also called cerebellar primitive neuroectodermal tumor (PNET)
    • Ependymal tumors are rare types of brain or spinal cord tumors

    Brain tumors in young children tend to grow quickly and can spread into the fluid that surrounds the brain and spinal cord. Radiation therapy given to the entire central nervous system works well in killing cancer cells, but it causes problems with thinking, learning and growing in young children. More treatment options are needed to avoid or lower the amount of radiation delivered to the brain and spinal cord to reduce the effects of brain tumor treatment in young children.

    Using new information learned from previous St. Jude brain tumor clinical trials, researchers have found a new way to improve outcomes for children younger than age 3 years.

    • This treatment includes intense chemotherapy as well as carefully planned use of smaller, more focused doses of radiation therapy given earlier in the treatment plan. The use of more focused radiation allows for less radiation to be delivered to surrounding healthy brain tissue.

    Purpose of this clinical trial

    The purpose of SJYC07 is to try to improve on the standard brain tumor treatment for young children.

    Treatment

    All participants in this study will be treated with a combination of chemotherapy (anti-cancer drugs).

    • Combination chemotherapy kills cancer cells and is used on this trial to avoid or reduce the amount of radiation given to young children.  Also, by starting with chemotherapy, the brain is given more time to develop before radiation is given.
    • One of the chemotherapy drugs used in this study is methotrexate.
      • This drug was studied in two previous clinical trials and was found to improve cure rates for children less than 3 years of age with medulloblastoma
    • Most participants treated in this trial will also receive radiation therapy, which is carefully targeted to the tumor.
      • This targeted type of radiation may result in fewer problems with thinking and learning than radiation to the whole brain and spinal cord.

    Eligibility overview

    • Newly diagnosed brain tumor or tumor of the central nervous system and less than 3 years of age
    • Children between 3 and 5 years old with medulloblastoma  that has not spread  into the fluid that surrounds the brain and spinal cord can also be treated on this trial
    • No prior radiation or chemotherapy
  3. SJYC07 Quick View
    Sponsor St. Jude Children’s Research Hospital
    Collaborator University of Florida and National Cancer Institute (NCI)
    ClinicalTrials.gov identifier NCT00602667
    Trial start date November 2007
    Estimated enrollment 315
    Study type Interventional
    Study phase Not provided
    Conditions Brain and central nervous system tumors
    Ages
    Up to 5 years
    Principal investigator Amar Gajjar, MD
    Study sites
    St. Jude Children's Research Hospital and collaborating sites in the U.S. and Australia
    For a consultation or to discuss SJYCO7 St. Jude Brain Tumor Program
    Phone: 901-595-2544 or 901-595-4599
    Fax: 901-595-6211

Contact

Amar Gajjar, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.