This lay summary is intended to provide a general overview of the Children’s Oncology Group study # ACNS 0332. It will provide information about the children that are eligible for this study and basic information regarding the specifics of the study. The informed consent and protocol contain the full details of the study. Those documents are available to you from your oncologist.

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 healthcare team in any way. You can find additional information about participation on clinical trials on CureSearch.org.Always discuss any questions that you may have with your healthcare team.

Brief Title:ACNS0332 is A Phase III study for patients with high risk Medulloblastoma and/or PNET

Official Title:ACNS0332-Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients

Trial Opening Date: March 26, 2007

A total of 300 eligible patients will take part in this study. It is expected to take 5 years to enroll this number of patients.

General Patient Eligibility:

Please consult your doctor to determine whether this is an appropriate study for your child

Patient Age:Greater than or equal to 3 and less than 22 years of age at diagnosis

For patients with:

• Newly diagnosed, previously untreated Medulloblastoma with some of the tumor left after surgery
• Tumor cells present in spinal fluid
• Tumor present in another area(s) of the brain away from the primary tumor location
• Tumor present in the spine
• Anaplastic Medulloblastoma
• Patients must meet organ function criteria. This means results of tests for liver, kidneys and bone marrow function must meet levels identified in the study

Patients with the following may not be eligible:

• Patients with Medulloblastoma present outside of the brain and/or spine
• Patients taking Isotretinoin (accutane) for acne must discontinue drug use for this condition prior to enrollment
• Prior chemotherapy or radiation

Enrollment criteria:

• Patient must be enrolled on the study prior to beginning therapy.
• Must be started on protocol within 31 days of the initial surgical procedure
• Patients with an allergies to parabens (preservative in Isotretinoin capsule) or soybeans (Isotretinoin is suspended in soybean oil in the capsule) will be randomly assigned to a regimen without Isotretinoin

You will find additional information about the staging of Medulloblastoma on CureSearch.org

General Background and Study Goal

The overall goal of this study is to compare the effects, good and/or bad, of the chemotherapy drugs carboplatin and isotretinoin on subjects with high risk medulloblastoma and to find out if one or both are better than standard therapy alone.

The purpose of this study is:

• To find out if giving the drug carboplatin along with radiation therapy is more effective than giving radiation therapy alone.
• To find out if the drug isotretinoin can improve the survival of subjects with high risk medulloblastoma.
• To measure any effects that the different types of treatment have on the quality of life (general well-being).
• To measure the brain function of subjects (measuring intelligence, memory, language, nonverbal skills, attention, and academic achievement) and the relationship between level of brain function and their quality of life.

Another purpose of the study which is optional is:

• To identify markers in the DNA of tumor tissue that will help us know how best to treat patients in the future and to pick the most promising new therapies for future studies.

Summary of the Treatment

This is a randomized study that compares four different treatments. It is not yet known which treatment will be better. The “arm” or version of treatment a patient receives is determined by a computer. You will find additional information about clinical trials on CureSearch.org.

The treatment will begin within 31 days after your surgery (to remove the tumor) and will involve both radiation therapy and chemotherapy. The treatment takes either 9 or 15 months and is divided into 2 or 3 stages (depending on the treatment arm you are randomized to).

The first stage of therapy is called Chemoradiotherapy. Everyone receives a combination of radiation therapy and chemotherapy to kill the cancer cells that are left over after surgery. This part of therapy will take 6 weeks. Some patients will have an extra chemotherapy medicine added to this treatment phase which they will receive every day they get radiation therapy in addition to a medicine given to everyone once a week. Both medicines are given IV.

In the second stage of therapy, called Maintenance, Everyone receives a combination of chemotherapy medicines. Maintenance therapy will last 6 months. The goal of maintenance therapy is to kill any remaining cancer cells that are left over from Chemoradiotherapy. Some patients will have an extra chemotherapy medicine added to the chemotherapy medicines during this stage which is taken by mouth.

Only some patients will go onto a third stage of therapy, called Continuation. Continuation therapy will consist of 6 more months of therapy with one medicine that you take by mouth.

Risks and Side Effects

Chemotherapy can cause short- and long-term side effects. All patients will be closely monitored to reduce the likelihood of negative side effects. All risks and side effects will be explained in detail by your healthcare team during the consent process. They can answer any questions that you may have regarding participation on the clinical trial or other aspects of care. Please refer to the consent document for a detailed explanation of the side effects associated with the treatment on this study.

Contact information

Your child’s oncologist is the best source for further information. Physicians with eligible patients should refer questions to the principal investigator:

James Olson, MD