A Phase II Trial of Conformal Radiation
Therapy for Pediatric Patients with Localized Ependymoma, Chemotherapy Prior
to Second Surgery for Incompletely Resected Ependymoma, and Observation for
Completely Resected Differentiated, Supratentorial Ependymoma Description: The study attempts to define a standard
for treatment of intracranial ependymoma based on tumor location, degree of
resection, and histological characteristics. Treatment will fall into one of
four groups. The study will include children under 3 years of age for treatment
with conformal radiation. Eligibility: Patients must be > 12 months and
< 21 years of age at time of enrollment. Patients must have had no prior
treatment except previous surgery or corticosteroid therapy. Target tumors:
histologically confirmed intracranial ependymoma. Patients with differentiated
or anaplastic ependymoma are eligible. (Patients with primary spinal cord ependymoma,
myxopapillary ependymoma, subependymoma, ependymoblastoma, or mixed gliomas
are not eligible.) Study Design: Phase II clinical trial with four
treatment arms, based on tumor location, degree of resection, and histology. Contact: Joanne M. Hilden, M.D., at 216-444-8407
or Bruce H. Cohen, M.D., at 216-444-9182.
Gliomas
Recurrent High-Grade Glioma A Phase II
Study of R115777 (Zarnestra) (NSC# 702818, IND# 58359) in Children with Recurrent
or Progressive High-Grade Glioma, Medulloblastoma/ PNET, or Brainstem Glioma Description: The protocol tests effectiveness
of investigational drug R115777 (Zarnestra) in treating recurrent malignant
childhood brain tumors. Eligibility: Patients must be <= 21 years of
age at time of enrollment. Target tumors: recurrent or progressive anaplastic
astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma,
recurrent or refractory medulloblastoma/PNET, or diffuse intrinsic brainstem
glioma. Patients must have histopathologic verification of diagnosis from either
initial presentation or at time of recurrence except for brainstem glioma patients.
Patients must have radiographically documented measurable disease and have relapsed
or become refractory to conventional therapy. Patients must have life expectancy
of at least 8 weeks. Patients are excluded for uncontrolled infection, allergy
to azoles, or for taking enzyme-inducing anticonvulsants. Study Design: Phase II. Patients receive study
drug for 21 days followed by 7-day rest period. The 28-day cycles may be repeated
for up to two years in the absence of disease progression or unacceptable toxicity. Contact: Joanne M. Hilden, M.D., at 216-444-8407
or Bruce H. Cohen, M.D., at 216-444-9182.
High-Grade Glioma A Phase II Study of Temozolomide
in the Treatment of Children with High-Grade Gliomas Description: The protocol tests the effectiveness
of FDA-approved temozolomide combined with radiation therapy against hard-to-treat
high-grade gliomal brain tumors. Eligibility: Patients must be >= 3 years of
age and < 22 years of age at time of enrollment. Target tumors: anaplastic
astrocytoma, glioblastoma multiforme, gliosarcoma. Patients must have histologic
verification of diagnosis. Patients with primary spinal cord malignant gliomas
are also eligible. Metastatic disease-ineligible. Study Design: Phase II. Initially patients receive
temozolomide concurrently with radiation therapy on 42-day schedule. Four weeks
after radiation therapy, patients receive temozolomide daily for 5 days, beginning
a new cycle every 28 days; 10 cycles total. Contact: Joanne M. Hilden, MD 216-444-8407
R115777 (Zarnestra) in Recurrent High-Grade
Gliomas Description: The protocol tests effectiveness
of investigational drug R115777 (Zarnestra) in treating recurrent malignant
childhood brain tumors. Eligibility: Patients must be > 21 years of
age at time of enrollment. Target tumors: recurrent or progressive anaplastic
astrocytoma, glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma,
recurrent or refractory medulloblastoma/PNET, or diffuse intrinsic brainstem
glioma. Patients must have histopathologic verification of diagnosis from either
initial presentation or at time of recurrence except for brainstem glioma patients.
Patients must have radiographically documented measurable disease and have relapsed
or become refractory to conventional therapy. Patients must have life expectancy
of at least 8 weeks. Patients are excluded for uncontrolled infection, allergy
to azoles, or for taking enzyme-inducing anticonvulsants. Study Design: Phase II. Patients receive study
drug for 21 days followed by 7-day rest period. The 28-day cycles may be repeated
for up to two years in the absence of disease progression or unacceptable toxicity. Contact: Joanne M. Hilden, M.D., at 216-444-8407
or Bruce H. Cohen, M.D., at 216-444-9182.
CCG-A9952 Chemotherapy For Progressive
Low Grade Astrocytoma in Children Less Than Ten Years Old Description: Children less than 10 years old
(120 months) with low-grade astrocytomas (grade 1 and 2) or other low grade
gliomas who have progressive disease following surgical excision, or an incomplete
excision (< 95% or > 1.5 cm 2 residual tumor) with necessity to begin
treatment because of a risk of neurologic impairment with progression. Study Design: Phase III trial, two randomized
regimens with NF-1 patients non-randomly assigned. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce
H. Cohen, MD 216-444-9182
CCG-99703 A Pilot Study of Intensive Chemotherapy
with Peripheral Stem Cell Support for Infants with Malignant Brain Tumors Study
Design: Pilot study, chemotherapy with collection of PBSC followed by three
cycles of high dose chemo with PBSC rescue. Eligibility: All children greater than 180 days
and less than 36 months of age at diagnosis. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce
H. Cohen, MD 216-444-9182
Refractory Low-Grade Glioma A Phase II
Study of Vinblastine Sulphate Injection in Children with Recurrent or Refractory
Low-Grade Glioma Description: The protocol investigates whether
the maximally tolerated dose of vinblastine would delay or perhaps obviate need
for radiation or aggressive surgery in children with recurent or refractory
low-grade gliomas. Eligibility: Patients must be < 21 years of
age at original diagnosis. Patient must show unequivocal evidence of tumor recurrence
or progression by Gd-MRI or contrast-enhanced CT scan. Target tumors include:
low-grade astrocytoma, pilocytic astrocytoma, pleomorphic xanthoastrocytomas,
subependymal giant cell astrocytoma, infantile desmoplastic astrocytoma, low
grade oligodendrogliomas, low-grade oligoastrocytoma, and chiasmatic-hypothalamic
tumor. Study Design: Phase II internal protocol (IRB
5962) Contact: Joanne M. Hilden, MD 216-444-8407
Miscellaneous
CCG-99701 An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed By Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors Study Design: This is a phase I/II pilot study evaluating the feasible dose and duration of concurrent carboplatin given with craniospinal radiation therapy, followed by one of two randomized maintenance chemotherapy regimens. Eligibility: Patients must be =3 years and less than 22 years of age at the time of diagnosis. The target tumors are: posterior fossa PNET (M1-3 or M0 with > 1.5 cm 2 residual), non-posterior fossa PNET (M0-3), medulloepithelioma and atypical teratoid tumors (M0-3). Patients with M4 disease are not eligible. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
P9934 Systemic Chemotherapy, Second Look Surgery and Involved Field Conformal Radiation for Children >= 8 months and <=36 months with Non-metastatic (MO) Medulloblastoma Study Design: Phase III trial, no randomization Eligibility: Patients age > 8 months and < 3 years of age with a primary histologic diagnosis of medulloblastoma or posterior fossa primitive neuroectodermal tumor (PNET), with no evidence of metastases. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
P9963 A Phase II Trial of Rebeccamycin Analogue in Children with Solid Tumors including CNS (Brain) Tumors Description: A single agent phase II trial to determine the response to the Rebeccamycin Analogue (NSC #655649) in the treatment of children with refractory neuroblastoma, bone or soft tissue sarcomas, non-Hodgkin’s lymphoma, other solid tumors, or brain tumors. Eligibility: Patients less than 22 years, with histologically documented brain tumors who exhibit recurrent or refractory tumor growth will be eligible, eligible histologies being: 1) medulloblastoma/PNET; 2) Ependymoma; 3) Brainstem glioma. Patients must have measurable disease. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
P9962 Phase II Study of Intrathecal Topotecan in Patients with Refractory Meningeal Malignancies, A POG/CCG Intergroup Study Active 8/17/2001 Description: This protocol will investigate intrathecal topotecan given on a twice weekly schedule (every three to four days) in patients with refractory meningeal neoplasia. Drug administration may be either by the intraventricular (Ommaya reservoir injection) Study Design: Intrathecal topotecan will be administered on a twice weekly basis for a total of 6 weeks in induction. Patients may proceed to consolidation therapy if there is no evidence of disease progression. Intrathecal topotecan will be administered weekly for a total of 4 doses in consolidation. The first dose of consolidation will be given 1 week after the last induction dose. Intrathecal topotecan will be given twice monthly for four months and then monthly thereafter. The first dose of maintenance will be given two weeks after the last consolidation dose. The maximum duration of intrathecal topotecan treatment will be one year. Eligibility: Patients must be > 1 and < 21.99 years of age at study entry. Patients must have neoplastic meningitis from leukemia/lymphoma or solid tumor. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
P9761 A Phase II Trial of Irinotecan in Children with Refractory Solid Tumors: A POG/CCG Intergroup Study Description: A phase II trial to determine the efficacy of irinotecan in the treatment of children with refractory neuroblastoma, sarcomas of soft tissue or bone, other solid tumors, or brain tumors. Study Design: Irinotecan is give for 5 days every 21 days; all patients who demonstrate continued response or stable disease without significant toxicity may continue to receive therapy. Subsequent radiographic evaluations should be performed every 3 months and as clinically indicated. Eligibility: Patient must be > =1 at the time of study enrollment, and < or =21.99 years of age at the time of original diagnosis. Patients with histologically documented brain tumors who exhibit recurrent or refractory tumor growth will be eligible. Patients will be stratified based on tumor histology into the following groups: 1) medulloblastoma/PNET; 2) ependymoma; 3) brain stem; glioma 4) other CNS tumor. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
A09705 Phase II Evaluation of Intravenous
Navelbine (Vinorelbine) in Recurrent or Refractory Pediatric Malignancies Description: This phase II study will evaluate
the efficacy of Navelbine in the treatment of recurrent or refractory solid
and CNS tumors. Study Design: The drug is administered given
in 8 week courses that include weekly doses for 6 consecutive weeks followed
by a 2 week rest, for a maximum of 10 courses. Eligibility: CNS tumors eligible include Astrocytoma,
PNET/Atypical Teratoid/Rhabdoid tumors, and Ependymoma. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce
H. Cohen, MD 216-444-9182
CNS AT/RT A Single-Arm Open-Label Limited-Institutional
Phase II Study of Multi-Agent Intrathecal and Systemic Chemotherapy with Radiation
Therapy for Children <18 Years with Newly Diagnosed Central Nervous System
Atypical Teratoid/Rhabdoid Tumor Description: The study represents a multi-institutional
effort to estimate activity of an aggressive multimodality regimen for highly
malignant atpyical teratoid-rhabdoid tumors of the CNS. Treatment showed promising
results in a very limited number of these extremely rare cases. Favorable study
results may occasion a full-scale national trial proposal. Eligibility: Patients must be < 18 years of
age. Target tumors: histologically confirmed primary intracranial CNS AT/RT
or tumor that possesses the INI1 gene mutation. Study Design: Phase II internal trial (IRB 6140) Contact: Joanne M. Hilden, MD 216-444-8407; or
Bruce H. Cohen, MD 216-444-9182
Biology Studies
CCG B961 Prognostic Significance of Ki-67 Proliferative Index Utilizing the MIB-1 Antibody in Low Grade Gliomas in Young Children Description: A biology study to determine the value of the Ki-67 proliferative index utilizing the MIB-1 antibody in predicting time to progression in low grade gliomas in young children following: (a) initial diagnosis, and (b) at time of tumor progression, if surgery is performed. Study Design: Unstained slides are sent to COG at the time of study entry. Eligibility: Patients entered on CCG 9952 Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
CCG B 971 Molecular Cytogenetic Determination of Prognostic Parameters in Childhood Primitive Neuroectodermal Tumor Description: Biology study to correlate molecular and cytogenetic findings with outcomes on COG clinical trials. Study Design: Tissue is accessed at the time of study entry. Eligibility: study: all patients less than 21 years of age with a primary CNS malignancy consistent with PNET/MB, or ATT/Rh, who are entered on CCG front-line studies. Patients can not have received any prior radiation treatment before the tissue was obtained. Study credit will be given for specimens obtained retrospectively on closed CCG studies, providing they are adequate for analysis. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
CCG B947 Protocol for Collection of Biology Specimens for Research Studies Description: Specimen accrual system for cytogenetic and molecular biologic studies of childhood tumors. Study Design: Tissue is sent at the time of surgery, either primary, or at second look. Eligibility: All surgical patients age < 21 years, any neoplastic histology. Contact: Joanne M. Hilden, MD 216-444-8407, Bruce H. Cohen, MD 216-444-9182
Miscellaneous
