Pilot Study of Systemic and Intrathecal Chemotherapy Followed by Conformal Radiation for Infants With Brain Tumors
All children in the study will receive Regimen 1 chemotherapy. Children whose tumor is
limited to one area at the beginning of the study will go on to have radiation therapy and
then Regimen 2 chemotherapy. Children whose tumor was found in more than one part of the
brain or in the cerebrospinal fluid at the beginning of the study will discontinue their
treatment on this protocol after Regimen 1 chemotherapy.
Regimen 1 Chemotherapy - Those children with a normal CSF flow study at the beginning of the
study will receive Regimen 1 chemotherapy along with mafosfamide. Those children with an
abnormal CSF flow study will receive Regimen 1 without mafosfamide and a repeat CSF flow
study will be performed at the completion of the first 10 weeks of treatment. If the CSF
study reflects normal CSF flow, then intrathecal mafosfamide will be given during the second
10 weeks of Regimen 1. Regimen 1 is divided into two courses. Each course lasts about 10
weeks, for a total of 20 weeks of treatment. During Regimen 1 the patient will receive three
medications (cyclophosphamide, vincristine, and cisplatin) that are given through the
central venous line. The patient will also receive one medication that is given by mouth
(etoposide). Cyclophosphamide, vincristine, cisplatin, and etoposide are all anticancer
drugs that have been useful in the treatment of brain tumors.
The experimental drug, mafosfamide, will be injected into the spinal fluid. This will be
given through either a spinal tap, the Ommaya reservoir, or both. Alternating mafosfamide
between the spinal tap and the Ommaya reservoir may improve how well the drug works by
making sure it spreads throughout the spinal fluid. If the patient has a VP or VA shunt (
specialized devices that relieve the pressure inside the head that comes from a block in the
normal flow of spinal fluid), then the patient will not receive an Ommaya reservoir, and all
doses of mafosfamide will be given through a spinal tap only.
The starting dose of mafosfamide will be a dose that has been safely given to older
children. If that dose does not cause severe side effects, the next group of patients will
receive a higher dose of mafosfamide. If severe side effects occur, the next group of
patients will receive a lower dose of mafosfamide
During and at the end of Regimen 1, the patient will be evaluated for response of the brain
tumor to treatment. A second operation may be necessary to remove more of the brain tumor.
Children whose tumor had spread at the time they began this study have completed treatment
at this point. Children whose tumor had not spread at start of the study will begin
radiation therapy, if their tumor appears to be unchanged or shrinking after Regimen 1.
Radiation Therapy - The dose, location, and timing of radiation will depend on the age of
the child at diagnosis, the location of his/her tumor, and the response of his/her tumor to
Regimen 1 chemotherapy. The radiation treatments used in this protocol are designed in an
attempt to reduce some of the side effects that usually occur after standard radiation
The child will receive radiation using a new technology called "conformal radiation".
Conformal radiation is designed to reduce the amount of normal brain tissue that is exposed
to high doses of radiation.
Regimen 2 Chemotherapy - After radiation therapy,the patient will receive additional
chemotherapy, which will last about 20 weeks. Regimen 2 chemotherapy is the same as the
Regimen 1 chemotherapy, except that the patient will not be given the drugs cisplatin and
Pharmacokinetic (PK) studies will be performed with a total of 2 doses of intrathecal
mafosfamide. PK studies tell us how the patient's body handles the study drug, mafosfamide.
Sampling times (times when we collect cerebrospinal fluid for the PK studies) will be prior
to drug administration and at 10 minutes, 2 hours, and 4 hours following drug
administration. These studies will be performed after one dose of drug given through the
spinal tap and after one dose of drug is given through the Ommaya reservoir. The
pharmacokinetic study is optional and you can choose not to allow these samples to be drawn.
Refusing the pharmacokinetic study will not affect the patient's participation/treatment on
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the feasibility, including expected disease progression, of delivering 20 weeks of systemic chemotherapy plus (IT) mafosfamide.
Susan Blaney, MD
Baylor College of Medicine
United States: Food and Drug Administration
|St. Jude Children's Research Hospital||Memphis, Tennessee 38105-2794|
|Texas Children's Hospital||Houston, Texas|
|Brain Tumor Center at Duke University||Durham, North Carolina 27710|