Introduction

This summary is intended to provide a general overview of the Children's Oncology Group study # ACNS0331. It tells who can be in this study and other basic information. The informed consent and protocol contain the full details of the study. You can get those from your oncologist.

ACNS0331 is a Phase III clinical trial. A trial is another word for a study. This study (clinical trial) is a therapeutic clinical trial. That means it is done to learn more about how well treatments work and the side effects of the treatments. The purpose of a Phase III trial is to learn if a new treatment that is known to work in treating a type of cancer is better in some way than the standard treatment. For example, does it have better cure rates, longer control of disease, fewer or less serious side effects, or fewer days in the hospital?

ACNS0331 compares different doses and volumes of radiation therapy. These treatments are called study arms. Usually, one study arm is the standard or the best proven current treatment. The other study arms have some changes or additions. The new treatment is thought to be at least as good as the standard treatment. It is not known if the new treatment will be better or worse than the standard treatment.

In a Phase III trial, each child is assigned to a study arm by a method called randomization. This is a process like flipping a coin that assures that each child has a fair and equal chance of being assigned to any of the study arms. That way, the study arms can be compared fairly.

In most clinical trials, we will not know which treatment is best until all of the children taking part in the trial have completed treatment and have been followed for several years. If one of the treatments is found to be better or safer than the others while the trial is still on-going, the trial will be stopped. All children still in the trial will be given the treatment with the best results when possible.

It is important to understand that participating in a clinical trial is entirely voluntary. The decision about whether or not to participate will not affect the care provided by the health care team in any way. You can find additional information about participation in clinical trials at www.childrensoncologygroup.org Always discuss any questions that you may have with your health care team.

Study Number: ACNS0331

Official Title: A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18 Gy) and Chemotherapy in Children with Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

Trial Opening Date

ACNS0331opened on 4/12/2004. The studycommittee hopes to enroll 549 patients. It is expected that this study will remain open until this number of patients has been enrolled. This study does not have a set end date for enrollment.

General Patient Eligibility

• Diagnosis: posterior fossa medulloblastoma
• Age: 3-21* years old

*Enrollment for patients age 8 and older closed in January 2012

Please consult your doctor to determine whether your child may participate in this study.

General Background and Study Goal

Standard treatment for childhood medulloblastoma is surgery, followed by radiation, with chemotherapy. Radiation is given to the entire brain and spine, with an additional "boost" dose to the back of the brain, called the posterior fossa. This treatment has been effective in curing medulloblastoma in many children. However, radiation to the brain and spine can have serious long term side effects, especially in children younger than 8.

ACNS0331 will compare different ways of reducing radiation to certain children with medulloblastoma. Children younger than 8 will be randomized to receive the standard dose of radiation to the brain and spine (23.4 Gy) or a reduced dose (18 Gy). Patients 8 years of age and older will receive the standard dose of radiation. All patients will receive a boost to the area of the tumor, but all patients, regardless of age will be randomized to different "volumes" of radiation boost. Volume refers to the area of brain receiving radiation. In ACNS0331, some children will receive a boost dose to the entire posterior fossa, and some will receive radiation to the area of tumor bed, which is a smaller volume. Current standard treatment volume is the entire posterior fossa.

All children on the study will receive the same chemotherapy during and after radiation treatment.

Summary of the Treatment

Radiation will begin about 4 weeks after surgery. Radiation will be given five days a week for 6 weeks for all patients. The chemotherapy drug, vincristine, will be given once a week for 6 weeks during radiation.

Four weeks after radiation is complete, chemotherapy will begin. Chemotherapy is identical for all patients, and includes 6 cycles of lomustine, cisplatin and vincristine as well as 3 cycles of cytoxan and vincristine.

Special Considerations

Patients who are randomized to the lower dose cranial spinal radiation will receive 5.4 Gy boost to the posterior fossa, to make sure that all patients receive at least 23.40 Gy radiation to the posterior fossa.

If a patient takes part in ACNS0331 scientists will perform tests on some of the tumor removed during surgery. These tests are being done to better understand medulloblastoma tumor cells.

Optional Neuropsychological Tests and Quality of Life

We would like you and your child to participate in tests and questionnaires to learn how the treatment on this study is affecting your child's life and development. These tests and questionnaires are called neuropsychological tests and are offered to all patients with brain tumors. If you agree to participate, you will be asked to sign another consent form for ALTE07C.

Parents of children on this study are asked to complete some questionnaire and surveys to see how the treatment is affecting your child's life. These are called quality of life studies. The surveys are to be filled out at several different times during and after treatment. There will be no cost to you for completion of these measures and we will coordinate these tests at a time when you will be seen in clinic. Participating in this part of the study is optional.

Risks and Side Effects

Chemotherapy and radiation therapy can cause side effects during and after treatment. All patients will be closely monitored for possible side effects of the medicines. All risks and side effects will be explained by your treatment team during the consent process. They can answer any questions that you may have about giving permission for your child to be in the clinical trial or other aspects of care. Please refer to the consent form for a detailed explanation of the side effects associated with the treatment on this study.

Contact Information

Your child's oncologist and nurses are the best sources for further information.

 Study Chair:

Jeff Michalski, MD

Washington Univ. Medical Center

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS