Brief Title
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor
Official Title
Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed With Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation With Myeloablative Chemotherapy (Thiotepa, Etoposide and Carboplatin) and Autologous Stem Cell Rescue
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of different regimens of combination
chemotherapy followed by peripheral stem cell transplantation in treating children who have
newly diagnosed brain tumor.
Detailed Description
OBJECTIVES:
- Investigate the toxicity of and response rate to an intensification of an induction
chemotherapy regimen (regimen A: cisplatin, vincristine, cyclophosphamide, and
etoposide) by incorporation of high-dose methotrexate with leucovorin calcium rescue in
patients with primitive neuroectodermal tumors and evidence of leptomeningeal
dissemination (M1, M2, or M3).
- Investigate the toxicity of and response rate to a new dose intensive induction
chemotherapy regimen (regimen C: vincristine, carboplatin, and temozolomide) in children
under ten years of age who are newly diagnosed with either high grade gliomas or diffuse
intrinsic pontine tumors. (Regimen B closed to accrual effective 3/30/2000; regimen C
open to accrual effective 7/21/2000)
- Investigate the feasibility of utilizing regimen C chemotherapy followed by
consolidation with myeloablative chemotherapy and autologous stem cell (either bone
marrow and/or peripheral blood) rescue in these patients. (Regimen B closed to accrual
effective 3/30/2000; regimen C open to accrual effective 7/21/2000)
- Investigate the toxicity of and response rate to an intensification of induction regimen
A chemotherapy by incorporation of high-dose methotrexate with leucovorin calcium rescue
in patients with primitive neuroectodermal tumors and evidence of leptomeningeal
dissemination (M1, M2, or M3).
- Estimate the time to disease progression and the pattern of relapse in patients who do
not have radiographic or cytologic evidence of residual disease at the time of
consolidation chemotherapy and who, therefore, do not receive post consolidation
irradiation.
- Estimate the time to disease progression and the pattern of relapse in patients who have
radiographic or cytologic evidence of residual disease at the time of consolidation
chemotherapy and who, therefore, receive post consolidation irradiation.
- Assess the morbidity and mortality of the consolidation chemotherapy regimen following
either regimen C or the intensified regimen A in these patients. (Regimen B closed to
accrual effective 3/30/2000; regimen C open to accrual effective 7/21/2000)
- Assess the impact that irradiation avoidance or the administration of reduced volume
craniospinal and/or focused field local irradiation has on neuropsychometric,
endocrinological functions, and physical growth.
OUTLINE: This is a two regimen study based on disease characteristics.
Patients in regimens A, B, and C undergo leukapheresis after receiving filgrastim (G-CSF) by
subcutaneous (SC) injections.
- Regimen A: Patients without evidence of neuraxis dissemination receive five 21 day
courses of the following chemotherapy: cisplatin IV over 6 hours on day 0; etoposide and
cyclophosphamide IV over 1 hour on days 1 and 2; vincristine IV on days 0, 7, and 14 of
courses 1, 2, and 3; and G-CSF SC beginning on day 3 of each course and continuing until
blood counts recover or up to 48 hours before the start of the next course. Patients
with evidence of neuraxis dissemination also receive high-dose methotrexate IV over 4
hours on day 3 and leucovorin calcium orally or by IV bolus starting 24 hours prior to
methotrexate and continuing every 6 hours until methotrexate levels have diminished.
- Regimen B (closed to accrual effective 3/30/2000): Patients receive three 21-28 day
courses of the following chemotherapy: vincristine IV on days 0, 7, and 14 of each
course; carboplatin IV over 4 hours on days 3 and 4 of each course; oral procarbazine
daily on days 0-4; oral lomustine on days 3 and 4; and G-CSF SC daily beginning 24 hours
following the last dose of carboplatin and continuing until blood counts recover or up
to 48 hours before the start of the next course. On day 7 of each course, patients also
receive peripheral blood stem cell (PBSC) reinfusion following chemotherapy. Oral
lomustine is administered only for the first two courses.
- Regimen C (open to accrual effective 07/21/2000): Patients receive four 28 day courses
of the following chemotherapy: carboplatin IV over 4 hours on days 0 and 1 of each
course; vincristine IV on days 0, 7, and 14 of the first three courses only; oral
temozolomide daily on days 0-4; and G-CSF SC daily beginning on day 5 and continuing
until blood counts recover.
After regimen A, B, or C and in the absence of disease progression, patients undergo
consolidation myeloablative chemotherapy by receiving carboplatin IV over 4 hours on days -8,
-7, and -6, and then thiotepa IV over 3 hours followed by etoposide IV on days -5, -4, and
-3. Patients with malignant gliomas or unbiopsied diffuse intrinsic pontine tumors do not
receive etoposide. On day 0, patients are reinfused with autologous PBSC. Following recovery
from consolidation chemotherapy, patients with radiographic or cytologic evidence of residual
disease undergo radiotherapy.
Patients are followed at 3 months, then every 3 months for the first 2 years, then every 6
months for years 2-4, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 96 patients (73 for regimen A and 23 for regimen C) will be
accrued for this study. (Regimen B closed to accrual effective 3/30/2000.)
Study Phase
Phase 2
Study Type
Interventional
Condition
Brain and Central Nervous System Tumors
Intervention
filgrastim
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
0
Start Date
November 1997
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant, newly diagnosed brain tumor
Regimen A:
- Posterior fossa medulloblastoma/primitive neuroectodermal tumor (PNET):
- All stages, under 3 years at diagnosis OR
- High stage (local residual tumor postoperatively and/or neuraxis or extraneural
dissemination), 3-10 years at diagnosis
- Supratentorial PNET, pineoblastoma, cerebral neuroblastoma, ependymoblastoma,
medulloepithelioma, medullomyoblastoma:
- All stages, under 10 years at diagnosis
- Brainstem PNET:
- All stages, irrespective of extent of resection, under 10 years at diagnosis
- Ependymoma or anaplastic ependymoma:
- All stages, any location (except primary spinal cord ependymoma), under 3 years
at diagnosis OR
- Local residual tumor postoperatively and/or neuraxis dissemination, any location,
3-10 years at diagnosis
- Supratentorial ependymoma:
- All stages, irrespective of extent of resection, under 10 years at diagnosis,
excluding gross totally resected (confirmed by postoperative MRI) low grade
ependymoma not invading the ventricular system
- Metastatic retinoblastoma:
- Previously untreated (except for cryosurgery or laser surgery), under 10 years at
presentation of metastatic disease
- Primary atypical teratoid/rhabdoid tumors of the CNS:
- Under 10 years at diagnosis
- Choroid plexus carcinoma:
- Incompletely resected, all sites, under 10 years at diagnosis
Regimen C:
- Anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma,
anaplastic ganglioglioma, other anaplastic mixed gliomas:
- Under 10 years at diagnosis
- Diffuse intrinsic pontine tumors:
- Unbiopsied, under 10 years at diagnosis
The following diagnoses are not eligible:
- Myxopapillary ependymoma of the spinal cord, low grade brainstem astrocytoma, primary
CNS lymphoma or solid leukemic lesion (i.e., chloroma, granulocytic sarcoma), or
primary CNS germ cell tumor
PATIENT CHARACTERISTICS:
Age:
- Under 10 at diagnosis
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- Not specified
Hepatic:
- Bilirubin less than 1.5 mg/dL
- SGPT less than 2.5 times upper limit of normal
Renal:
- Creatinine clearance greater than 60 mL/min
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Prior corticosteroids allowed
- No concurrent corticosteroids for the sole purpose of antiemesis
Radiotherapy:
- No prior radiotherapy
Surgery:
- See Disease Characteristics
- Recovered from prior surgery
Gender
All
Ages
N/A - 10 Years
Accepts Healthy Volunteers
No
Contacts
Jonathan L. Finlay, MB, ChB, ,
Location Countries
Argentina
Location Countries
Argentina
Administrative Informations
NCT ID
NCT00003273
Organization ID
CDR0000066174
Secondary IDs
NYU-P9712
Responsible Party
Sponsor
Study Sponsor
NYU Langone Health
Study Sponsor
Jonathan L. Finlay, MB, ChB, Study Chair, NYU Langone Health
Verification Date
November 2015