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Clinical Trials (PDQ®)

Phase II Randomized Study of Induction with CTX/VCR/VP-16/CDDP vs IFF/VCR/VP-16/CBDCA Followed by Maintenance with CBDCA/VCR/CTX/VP-16, with Delayed Radiotherapy as Appropriate, in Infants with Previously Untreated Malignant Brain Tumors

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

Combination Chemotherapy Followed by Radiation Therapy in Young Children with Previously Untreated Brain Tumors

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentClosedunder 36 months at diagnosisNCICCG-9921

Objectives

I.  Estimate the response rate, freedom from progression, and toxicity 
experienced by children less than 36 months of age with newly diagnosed 
malignant CNS tumors treated with high-dose 
cyclophosphamide/vincristine/etoposide/cisplatin vs. 
ifosfamide/vincristine/etoposide/carboplatin given in conjunction with 
granulocyte colony stimulating factor.

II.  Estimate the disease-control interval using these two regimens without 
cranial irradiation in children who have no apparent residual tumor after 
initial surgery or who have had a complete response to induction chemotherapy 
(excluding those with metastatic disease at diagnosis).

III.  Estimate the disease-control interval using these two regimens with 
cranial irradiation to treat patients who have residual tumor following 
induction chemotherapy or metastatic disease at diagnosis.

IV.  Evaluate the feasibility of using a reduced dose of craniospinal 
irradiation (2,340 cGy) in children with nonmetastatic, nonprogressive 
medulloblastoma/PNET who require irradiation.

V.  Estimate the response rate, disease-control interval, recurrence-free 
survival, and overall survival of children treated with radiotherapy following 
disease progression on chemotherapy.

VI.  Determine whether clinical or biologic studies can predict response to or 
failure of chemotherapy, with a specific evaluation of the prognostic 
significance of tumor cell DNA content (ploidy).

VII.  Evaluate the tumor cytogenetic abnormalities in this group of children 
and correlate these abnormalities with histology and DNA content.

VIII.  Document the late effects (specifically cognitive function and 
endocrine function) of chemotherapy and radiotherapy in this patient 
population.

Entry Criteria

Disease Characteristics:


Histologically confirmed (except some brainstem tumors)
malignant brain tumors of the following types:
  PNET, including but not limited to:
     Medulloblastoma
     Pineoblastoma
     Cerebral neuroblastoma
     Ependymoblastoma
  High-grade astrocytoma, including:
     Glioblastoma multiforme
     Anaplastic astrocytoma
     Small cell glioblastoma
     Giant cell glioblastoma
     Gliosarcoma
  Ependymoma
  Choroid plexus carcinomas
  Malignant CNS germ cell tumors
  Primary sarcomas
  Brainstem glioma (selected)

Brainstem tumors may be either:
  Diffuse tumors (defined below) regardless of histology OR
  Localized histologically documented anaplastic gliomas

  Diffuse tumors are defined as:
     Poorly demarcated tumors on CT with intrinsic involvement
     (greater than 50% intra-axial) of the entire pons, the
     pons and the medulla, the pons and the midbrain, or the
     entire brainstem OR

     Tumors that on MRI intrinsically involve the pons, the
     pons and the medulla, the pons and the midbrain, or the
     entire brainstem

     Tumors involving the midbrain may also contiguously
     involve the thalamus or the upper cervical cord

     Histologic confirmation not required only if more than 50%
     of the tumor is intrinsic in brain stem

     The following tumors require biopsy-documented anaplastic
     histology:
        Tumors localized to midbrain alone on CT or MRI
        Tumors localized to cervicomedullary junction on CT or
           MRI
        Tumors with greater than 50% exophytic extension
           dorsally or laterally out of brainstem

The following tumors are specifically excluded:
  Pleomorphic xanthoastrocytoma
  "Desmoplastic ganglioglioma"
  Oligodendroglioma of any grade
  Ganglioglioma of any grade
  Low-grade astrocytoma
  Daumas-Duport Grade I and most Grade II tumors
  Cerebellar astrocytomas (except frank glioblastomas)
  Myxopapillary ependymomas of the spinal cord
  Neuraxial metastasis of histologically benign papillomas
  Low-grade brainstem astrocytoma
  Primary CNS lymphoma
  Leukemic solid brain tumors (i.e., chloromas, granulocytic
     sarcomas)

No more than 28 days between diagnostic surgery (or radiologic
diagnosis of brainstem tumor) and initiation of protocol
therapy


Prior/Concurrent Therapy:


No prior therapy


Patient Characteristics:


Age:
  Under 36 months at diagnosis

Performance status:
  Not specified

Hematopoietic:
  Not specified

Hepatic:
  Not specified

Renal:
  Not specified


Expected Enrollment

A total of 276 patients (up to 25 patients in each histologic category) will 
be accrued.  If no responses are seen in the first 14 patients treated in a 
given category, accrual in that category will cease.

Outline

Randomized study.  Patients are randomized for Induction on Arms I and II, 
then proceed to Maintenance.  Patients with residual disease following 
Induction, with metastatic disease at diagnosis, or those without prior 
radiotherapy who recur or progress receive further therapy on Regimen A.

Induction.

Arm I:  4-Drug Combination Chemotherapy with Urothelial Protection and 
Hematologic Toxicity Attenuation.  Vincristine, VCR, NSC-67574; Etoposide, 
VP-16, NSC-141540; Cisplatin, CDDP, NSC-119875; Cyclophosphamide, CTX, 
NSC-26271; with Mesna, NSC-113891; and Granulocyte Colony-Stimulating Factor 
(Amgen), G-CSF, NSC-614629.

Arm II:  4-Drug Combination Chemotherapy with Urothelial Protection and 
Hematologic Toxicity Attenuation.  VP-16; Carboplatin, CBDCA, NSC-241240; VCR; 
Ifosfamide, IFF, NSC-109724; with Mesna; and G-CSF.

Maintenance:  3-Drug Combination Chemotherapy alternating with 2-Drug 
Combination Chemotherapy with Urothelial Protection.  VCR; VP-16; CBDCA; 
alternating with VP-16; CTX; with Mesna.

Regimen A:  Radiotherapy.  Local tumor irradiation with, as appropriate, 
craniospinal irradiation, using Co60 or 4-15 MV photons.

Published Results

Leary SE, Zhou T, Holmes E, et al.: Histology predicts a favorable outcome in young children with desmoplastic medulloblastoma: a report from the children's oncology group. Cancer 117 (14): 3262-7, 2011.[PUBMED Abstract]

Geyer JR, Sposto R, Jennings M, et al.: Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 (30): 7621-31, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Cancer Group

Jeffrey Geyer, MD, Protocol chair
Ph: 206-987-6664

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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