Combination Chemotherapy, Radiation Therapy, and an Autologous Peripheral Blood Stem Cell Transplant in Treating Young Patients With Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentTemporarily closed21 and under at the time of definitive surgeryACNS0333
NCI-2009-00337, CDR0000592812, COG-ACNS0333, NCT00653068

Trial Description


This phase III trial is studying giving combination chemotherapy together with 3-dimensional conformal radiation therapy and an autologous peripheral blood stem cell transplant to see how well it works in treating young patients with atypical teratoid/rhabdoid tumor of the central nervous system. Giving high-dose chemotherapy before an autologous peripheral blood stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy or radiation therapy.

Further Study Information


I. To determine the 6-, 12-, and 24-month event-free survival and overall survival of children (birth to 21 years of age) with atypical teratoid/rhabdoid CNS tumors (AT/RT), diagnosed based on histology, immunophenotyping, and modern molecular and immunohistochemical analysis of INI1, treated with surgery, intensive chemotherapy combined with stem cell rescue, and radiation therapy.

II. To compare the outcome of very young patients (under 3 years old) on this study whose histologic diagnosis is AT/RT with infants identified as having AT/RT on POG-9233 and CCG-9921.


I. To determine the feasibility and toxicity of the proposed chemotherapy regimen in combination with radiation therapy.

II. To contribute tumor samples from which biologic and gene expression data can be developed to yield prognostic indicators and provide direction for future treatment strategies.

III. To develop a clinical and biologic database on which future studies can be based.

OUTLINE: This is a multicenter study. Patients are stratified according to age and tumor histology (infants [< 36 months of age] with tumor histology and immunohistochemical [IH] analysis diagnostic of atypical teratoid/rhabdoid CNS tumors [AT/RT] [stratum 1] vs infants with INI1 mutation only-based diagnosis [i.e., histology is not consistent with AT/RT] vs older children [≥ 36 months of age] with tumor histology and IH analysis diagnostic of AT/RT vs older children with INI1 mutation only-based diagnosis).

INDUCTION THERAPY AND STEM CELL HARVEST: Patients receive vincristine IV on days 1, 8, and 15 and high-dose methotrexate IV over 4 hours on day 1. Beginning 24 hours after the start of methotrexate, patients receive leucovorin calcium orally or IV every 6 hours until the serum methotrexate level is < 0.1 micromoles. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6*. Patients also receive filgrastim (G-CSF) IV or subcutaneously (SC) once daily beginning on day 7 and continuing until ANC recovers. When ANC is > 1,000/μL post nadir, patients receive G-CSF twice daily for stem cell mobilization. Approximately 2-4 days, later peripheral blood stem cells are harvested once daily, as needed, after each course of induction therapy until a total of 6 x 10^6 CD34+ cells/kg have been collected.

Treatment repeats every 21 days for 2 courses. After completion of induction therapy, patients are re-evaluated. Patients with progressive disease are removed from study. Patients with radiographic evidence of residual tumor are encouraged to undergo second-look surgery prior to proceeding to radiotherapy or consolidation therapy; patients with complete response, partial response, or stable disease proceed to radiation therapy or consolidation therapy depending on age, location of the tumor, and initial diagnosis (whether or not disease is disseminated).**

CONSOLIDATION THERAPY AND STEM CELL RESCUE: Within 2-6 weeks after completion of induction therapy or radiation therapy, patients begin consolidation therapy. Patients receive high-dose carboplatin IV over 4 hours and high-dose thiotepa IV over 2 hours on days 1 and 2 and undergo autologous peripheral blood stem cell (PBSC) rescue on approximately day 4. Patients also receive G-CSF IV or SC once daily beginning 24 hours after stem cell infusion and continuing until ANC recovers. Treatment with consolidation therapy followed by stem cell rescue repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

RADIATION THERAPY: *Before (but after induction therapy) or after consolidation therapy and stem cell rescue, patients undergo 3-dimensional conformal radiotherapy (3D-CRT) to the brain (and the spine if needed) 5 days a week for 5-6 weeks.

NOTE: *The administration of etoposide, cyclophosphamide, and cisplatin are dependant on the prior clearance of methotrexate to a level of < 0.1 micromoles.

NOTE: **Patients with localized posterior fossa tumors and ≥ 6 months of age at the end of induction therapy OR with localized supratentorial tumors at diagnosis and ≥ 12 months of age at the end of induction therapy proceed to radiotherapy followed by consolidation therapy; patients with disseminated disease at diagnosis, patients with localized posterior fossa tumors at diagnosis and < 6 months of age at the end of induction therapy, or patients with localized supratentorial tumors at diagnosis and < 12 months of age at the end of induction therapy proceed to consolidation therapy followed by radiotherapy. Previously collected tumor tissue is analyzed for a mutation in the INI1 rhabdoid tumor suppressor gene and stained for INI1 antibody.

After completion of study treatment, patients are followed periodically for up to 10 years.

Eligibility Criteria

Inclusion Criteria:

Diagnosis of CNS atypical teratoid/rhabdoid tumor (AT/RT) or tumors that have a mutation of the INI1 gene (even if the tumor does not have the usual histologic characteristics of AT/RT)

Patients with extra neural metastasis (M4) or renal rhabdoid tumors are not eligible

Patients with MRI evidence of spinal disease are eligible

Must have undergone definitive surgery in the past 31 days

Cranial MRI (with and without gadolinium) must be done pre-operatively

Post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery or 10-28days after surgery

Entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (10-28 days after surgery), prior to study enrollment (with and without gadolinium)

Life expectancy > 8 weeks

ANC > 1,000/μL

Platelet count > 100,000/μL (transfusion independent)

Hemoglobin > 8 g/dL (RBC transfusions allowed)

Creatinine clearance (minimum of 12-24 hour urine collection) or radioisotope GFR ≥ 60mL/min

Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

AST and ALT < 2 times ULN for age

Shortening fraction of ≥ 27% by echocardiogram OR ejection fraction of ≥ 47% by radionuclide angiogram

No evidence of dyspnea at rest

Pulse oximetry > 94% on room air

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

No prior radiotherapy or chemotherapy except for the following:

Patients enrolled on protocol ACNS0334 whose tumors demonstrate the INI1 gene mutation are eligible to transfer to this study even if they have received one course of induction therapy (these patients must be re-consented to treatment and restaged)

Prior corticosteroids allowed

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Childrens Oncology Group

  • National Cancer Institute
Alyssa Terry Reddy, Principal Investigator

Link to the current record.
NLM Identifier NCT00653068

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