IRB Number:

1617-04

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

This study is being done to:
- Find out if the overall dose of radiation to the brain and spine can be lowered without lowering rates of survival in children with medulloblastoma
- See if the volume of radiation given during the boost (extra radiation sent to the tumor area) can be lowered without lowering survival rates in children with medulloblastoma

Secondary goals of this study are to:
- Look at what characteristics are shared among children who are treated with a smaller amount of boost dose of radiation and have their cancer come back
- Look for the effects of lower radiation on children's hearing, ability to learn, and hormone function
- See if children given a smaller amount of boost dose radiation have fewer side effects to their hearing and hormone function compared to children that get the standard amount boost dose
- Develop a marker from the tumor's DNA that can tell how a child with medulloblastoma cancer may progress
.
Standard therapy for medulloblastoma includes surgery followed by radiation therapy (use of high-energy x-rays to kill cancer cells) to the brain and spinal cord with or without chemotherapy (treatment with anti-cancer drugs).

Recent studies using a combination of chemotherapy and radiation therapy to treat children with standard risk medulloblastoma have been 70 and 80 percent effective in curing this disease. However, many children have long-term side effects from radiation therapy to the brain and spine, including hearing loss, changes in hormone function (which can impact growth and sexual development), and learning problems (especially in younger children).

This study will look at what will happen if a smaller amount of radiation therapy is given to the brain and spinal cord of children with medulloblastoma. Some patients on this study will be given a standard dose of radiation and others will get a lowered dose.

This study will also look at what will happen if the amount of radiation that is given during the "boost dose" of radiation is lowered. Some patients on this study will be given a standard-amount boost, which means that the radiation is aimed at the entire area at the back of the brain. Other patients will be given a smaller amount boost which means that they will be given radiation aimed more directly to the tumor bed. All patients on this study will be treated with chemotherapy during and after radiation therapy.

Who is Eligible to Participate in the Study?

-Age 3 through 22
-Diagnosed with medulloblastoma, which is a type of childhood brain tumor
-The cancer is thought to be standard risk because the patient is over three years of age, the tumor is in the very back of the brain in an area called the posterior fossa, all or almost all of the tumor was taken out by surgery, and the cancer has not spread to other parts of the body.
-Patients must have no previous radiotherapy or chemotherapy other than corticosteroids.

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

In order to compare the effects of different doses and amounts of radiation, patients will be randomized to radiation treatment plans at the time of study entry. Children ages 3-7 will be randomized twice. They will be randomized between two doses of craniospinal radiation and between a standard volume boost and a smaller volume boost. All children eight years and older will be given the standard dose of craniospinal radiation and will only be randomized for the boost volume of radiation. Randomization is a computerized selection process that will be used to put patients to the study groups. The patient will be put in one of two groups by chance (as in the flip of a coin). Neither they nor their doctor will choose which treatment the patient will be given. The patient will have an equal chance of being assigned any of the treatment plans. If one treatment plan is found to be better, all children will be put on that treatment plan.

Chemoradiotherapy
Chemoradiotherapy begins about four weeks after surgery.

Radiation Therapy
Radiation therapy to the brain and spine will be given five days each week for six weeks.

Chemotherapy
V = Vincristine will be given directly into the vein (for less than a minute) once a week for six weeks beginning at Week 1 (one week after the start of radiation).

Maintenance Chemotherapy
Maintenance chemotherapy begins four weeks after the completion of chemoradiotherapy.
There will be nine cycles of maintenance. There are two different kinds of cycles given.
They are referred to as Cycle A and Cycle B. Cycle A lasts for six weeks and Cycle B lasts for four weeks. The B cycles are given after the completion of two A cycles. Below are the details of the drugs and schedules for A and B cycles.

Cycle A (This cycle lasts 42 days)
CCNU is given by mouth on Day 1.
Vincristine is given directly into a vein over a few seconds on Days 1, 8, and 15.
Cisplatin is given directly into a vein over eight hours on Day 1

Cycle B (This cycle lasts 28 days)
Cyclophosphamide is given into a vein over one hour on Days 1 and 2.
MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at three and six hours.
Vincristine is given directly into a vein over a few seconds on Days 1 and 8.

Chemotherapy can cause a patient's white blood cell count to be too low. White blood cells are infection-fighting cells and if their white blood cell count is low for too long, the patient will be given a drug called G-CSF. G-CSF is a growth factor naturally made in the body to stimulate the production of white blood cells. G-CSF can now be made in the laboratory and given to patients at higher doses than the body makes.

Before treatment on this study begins and while getting treatment, patients will have the following standard medical tests:
- Physical exam
- Blood tests
- Tests of kidney function
- Tests of liver function
- Tests of hormone function
- Hearing tests
- Magnetic Resonance Imaging (MRI) of brain and spine. (MRI uses magnetic waves to look at soft tissues of the body.)
- Evaluation of cerebral spinal fluid (CSF) obtained by lumbar puncture

How long will the Study run?

Patients will be in the study for about 14 months. However, they will keep on having physical exams, tests of hormone function, MRIs, hearing tests, blood tests, neurological tests, and tests of cognitive ability and quality of life for a few years after treatment so that the study doctors can keep on looking at any effects of treatment. After that, the study doctors would like to collect some general health information about the patient for as long as they will let us.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 12/29/2004

IRB Review and Approval Date: 08/19/2004

Study Type: Treatment

Projected Accrual: The plan is to have up to 600 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Carola Arndt, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 05/07/2008