Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors
NCT ID: NCT00392886
Last Updated: 2013-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
120 participants
INTERVENTIONAL
2004-03-31
Brief Summary
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PURPOSE: This phase III trial is studying how well giving combination chemotherapy with or without etoposide followed by an autologous stem cell transplant works in treating young patients with previously untreated malignant brain tumors.
Detailed Description
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Primary
* Determine the 2-year event-free survival (EFS) and overall survival (OS) of pediatric patients with previously untreated nondisseminated medulloblastoma (\< 4 years of age), disseminated medulloblastoma (\< 10 years of age), or noncerebellar primitive neuroectodermal tumors (PNET) (disseminated or non-disseminated) treated with induction chemotherapy followed by consolidation with myeloablative chemotherapy and autologous hematopoietic stem cell rescue.
* Determine the toxicity of this regimen in these patients.
* Determine the mortality of patients treated with this regimen.
Secondary
* Determine the complete and partial response rates after completion of induction chemotherapy in these patients stratified according to pathology (medulloblastoma vs noncerebellar PNET vs high-grade gliomas vs atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical papillomas vs ependymomas).
* Describe the EFS and OS of these patients stratified according to additional diagnoses (atypical teratoid/rhabdoid tumors vs choroid plexus carcinomas and atypical choroid plexus papillomas vs ependymomas vs high-grade gliomas).
* Describe the time to progression and patterns of relapse in these patients stratified by diagnosis and radiotherapy received (\< 6 years of age with evidence of no residual tumor pre-transplant and no post-transplant consolidation radiotherapy vs \< 6 years of age with residual tumor present pre-transplant treated with post-transplant consolidation radiotherapy vs \> 6 years of age treated with post-transplant consolidation radiotherapy).
* Determine the neuropsychometric function, endocrinologic function, and physical growth in these patients stratified according to radiotherapy received (none vs reduced-volume craniospinal radiotherapy vs focused local-field radiotherapy).
OUTLINE: This is a pilot study. Patients are stratified according to type of tumor (nonglial vs glial and diffuse pontine).
* Regimen C (patients with glial tumors):
* Stem cell harvesting (bone marrow and/or peripheral blood): Patients undergo leukapheresis or bone marrow aspiration to collect bone marrow or peripheral blood stem cells prior to beginning induction chemotherapy or after the first course of induction chemotherapy.
* Induction chemotherapy: Patients receive vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with unresectable bulky disease and corticosteroid dependence are removed from study. All other patients proceed to consolidation chemotherapy.
* Consolidation chemotherapy: Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3.
* Autologous bone marrow or peripheral blood stem cell transplantation: Patients undergo reinfusion of bone marrow or peripheral blood stem cells on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
* Radiotherapy: Beginning within 6 weeks after stem cell transplantation, patients \> 6 years of age at diagnosis undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients ≤ 6 years of age undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.
* Regimen D2 (patients with nonglial tumors):
* Stem cell harvesting (bone marrow and/or peripheral blood): Patients undergo leukapheresis or bone marrow aspiration to collect bone marrow or peripheral blood stem cells prior to beginning induction chemotherapy or after the first course of induction chemotherapy.
* Induction chemotherapy:
* Courses 1, 3, and 5 (28 days per course): Patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Patients also receive vincristine IV on days 1, 8, and 15 of courses 1 and 3.
* Courses 2 and 4 (28 days per course): Patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients also receive vincristine IV on days 1, 8, and 15 of course 2.
Patients with unresectable bulky disease and corticosteroid dependence are removed from study. All other patients proceed to consolidation chemotherapy.
* Consolidation chemotherapy: Patients receive carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours and etoposide IV over 3 hours on days -5 to -3.
* Autologous bone marrow or peripheral blood stem cell transplantation: Patients undergo re-infusion of bone marrow or peripheral blood stem cells on day 0. Patients also receive G-CSF SC beginning on day 1 and continuing until blood counts recover.
* Radiotherapy:Patients undergo radiotherapy as in regimen C. Patients in both regimens undergo neuropsychological testing after induction chemotherapy but before consolidation chemotherapy and then at 18, 36, and 54 months after completion of study treatment. Neuropsychometric and neuroendocrine testing is performed before and after radiotherapy. Quality of life is also assessed periodically.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Conditions
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Keywords
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Study Design
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TREATMENT
Study Groups
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Regimen C
Patients receive induction therapy of vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive consolidation therapy of carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3, undergo reinfusion of bone marrow or peripheral blood stem cells on day 0, and receive G-CSF SC beginning on day 1 and continuing until blood counts recover. Beginning within 6 weeks after transplantation, some patients undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity and some patients undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.
carboplatin
Given IV
temozolomide
Given orally
thiotepa
Given IV
vincristine sulfate
Given IV
autologous bone marrow transplantation
Given on day 0
autologous hematopoietic stem cell transplantation
Given on day 0
peripheral blood stem cell transplantation
Given on day 0
radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.
Regimen D2
In courses 1, 3, and 5, patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, vincristine IV on days 1, 8, and 15 (in courses1 and 3), and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In courses 2 and 4, patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, vincristine IV on days 1, 8, and 15 (in course 2), and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients receive consolidation therapy as in regimen C in combination with etoposide IV over 3 hours on days -5 to -3 and undergo autologous bone marrow or peripheral blood stem cell transplantation, receive G-CSF, and undergo radiotherapy as in regimen C.
carboplatin
Given IV
cisplatin
Given IV
cyclophosphamide
Given IV
etoposide
Given IV and orally
methotrexate
Given IV
temozolomide
Given orally
thiotepa
Given IV
vincristine sulfate
Given IV
autologous bone marrow transplantation
Given on day 0
autologous hematopoietic stem cell transplantation
Given on day 0
peripheral blood stem cell transplantation
Given on day 0
radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.
Interventions
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carboplatin
Given IV
cisplatin
Given IV
cyclophosphamide
Given IV
etoposide
Given IV and orally
methotrexate
Given IV
temozolomide
Given orally
thiotepa
Given IV
vincristine sulfate
Given IV
autologous bone marrow transplantation
Given on day 0
autologous hematopoietic stem cell transplantation
Given on day 0
peripheral blood stem cell transplantation
Given on day 0
radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.
Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed malignant brain tumor, including any of the following:
* Posterior fossa medulloblastoma/primitive neuroectodermal tumor (PNET)\*
* All stages allowed
* Must be \< 4 years of age at diagnosis unless there is evidence of postoperative residual tumor (\> 1.5 cm² tumor area) or evidence of neuraxis or extraneural dissemination (high-stage)
* Medulloblastoma, cerebral neuroblastoma, and ependymoblastoma allowed
* Low-stage (standard-risk) medulloblastoma not allowed in patients \> 4 years of age
* Ependymoma\*
* All stages and locations allowed
* Cellular and anaplastic subtypes allowed (no myxopapillary ependymomas of the spinal cord)
* Must be \< 36 months of age at diagnosis for posterior fossa tumor OR \< 72 months of age for supratentorial tumor
* Evidence of neuraxis dissemination irrespective of primary site
* No cellular (low-grade) supratentorial ependymomas at any age with complete resection of parenchymally based (i.e., not periventricular) supratentorial tumors
* Brain stem tumor\*
* All stages allowed irrespective of extent of resection
* No unbiopsied diffuse intrinsic pontine tumor
* Tumor pathologically confirmed to be either malignant glioma or PNET allowed
* High-grade glioma\*\*
* Primary atypical teratoid/rhabdoid tumor of the CNS\*
* Choroid plexus carcinoma or atypical choroid plexus papilloma\*
* All stages and locations allowed
* Anaplastic astrocytoma\*\*
* Glioblastoma multiforme\*\*
* Anaplastic oligodendroglioma\*\*
* Anaplastic ganglioglioma\*\*
* Other anaplastic mixed gliomas\*\*
* Small-cell glioblastoma\*\*
* Giant-cell glioblastoma\*\*
* Gliosarcoma\*\*
* The following diagnoses or subtypes are not allowed:
* Choroid plexus papilloma
* Pineocytoma
* Low-grade mixed glioma
* Primary CNS germ cell tumor
* Primary CNS lymphoma
* Solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
* Pleomorphic xanthoastrocytoma, low grade
* Desmoplastic ganglioglioma
* Low-grade astrocytoma
* Previously untreated disease
* Has undergone definitive surgery within the past 42 days NOTE: \*Patients receive treatment according to regimen D2
NOTE: \*\*Patients receive treatment according to regimen C
PATIENT CHARACTERISTICS:
* Bilirubin \< 1.5 mg/dL
* ALT and AST \< 2.5 times upper limit of normal
* Creatinine clearance and/or glomerular filtration rate ≥ 60 mL/min
PRIOR CONCURRENT THERAPY:
* See Disease Characteristics
* No prior radiotherapy or chemotherapy
* Prior corticosteroids allowed
* No concurrent corticosteroids for antiemesis only
* No concurrent brachytherapy or electron radiotherapy
* No concurrent dairy products or grapefruit juice with temozolomide administration
10 Years
ALL
No
Sponsors
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Children's Hospital Los Angeles
OTHER
Responsible Party
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Childrens Hospital Los Angeles
Principal Investigators
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Jonathan L. Finlay, MB, ChB
Role: STUDY_CHAIR
Children's Hospital Los Angeles
Girish Dhall, MD
Role:
Children's Hospital Los Angeles
Kelley Haley, RN, BSN
Role:
Children's Hospital Los Angeles
Locations
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Phoenix Children's Hospital Outpatient Center
Phoenix, Arizona, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Mattel Children's Hospital at UCLA
Los Angeles, California, United States
Children's Hospital and Research Center Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
University of Chicago Comer Children's Hospital
Chicago, Illinois, United States
Riley's Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Tomorrows Children's Institute at Hackensack University Medical Center
Hackensack, New Jersey, United States
Schneider Children's Hospital
New Hyde Park, New York, United States
NYU Cancer Institute at New York University Medical Center
New York, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, United States
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Toledo Children's Hospital
Toledo, Ohio, United States
St. Vincent Mercy Medical Center
Toledo, Ohio, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
Christchurch Hospital
Christchurch, , New Zealand
Wellington Children's Hospital
Wellington, , New Zealand
Swiss Pediatric Oncology Group Bern
Bern, , Switzerland
Universitaets Kinderklinik
Bern, , Switzerland
Countries
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Other Identifiers
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CHLA-HEAD-START-III
Identifier Type: -
Identifier Source: secondary_id
CHLA-HSIII
Identifier Type: -
Identifier Source: secondary_id
CHLA-2004-020
Identifier Type: -
Identifier Source: secondary_id
CHLA-04.020
Identifier Type: -
Identifier Source: secondary_id
UMN-MT2004-06
Identifier Type: -
Identifier Source: secondary_id
CDR0000503990
Identifier Type: -
Identifier Source: org_study_id