Introduction

This summary is intended to provide a general overview of the Children's Oncology Group (COG) study ACNS0831. It tells who can be in this study and other basic information. The informed consent form has more details about the study. You can get this from your oncologist.

ACNS0831 is a therapeutic, phase III trial. Therapeutic trials are research studies done to determine the safety and effectiveness of a treatment for a particular disease. Most children with cancer are treated on Phase III therapeutic trials. Phase III trials test the standard treatment (current best) against promising alternatives that may increase cure rates or decrease side effects or long-term effects of treatment.

ACNS0831 is a Phase III clinical trial that compares two or more treatments (called study "arms"). Each treatment has been shown to be effective in other studies but these treatments have not yet been compared to each other. Usually, one treatment arm is the "standard" or the best proven current treatment. The other (new) treatment(s) have some changes or additions. Phase III trials are designed to find out whether a new treatment is better in some way than the standard treatment (for example, to find out if a new treatment cures the disease in more children, controls the disease longer, causes fewer or less serious side effects, or changes the number of days spent in the hospital).

To learn if one treatment in a Phase III clinical trial is better, each child is assigned randomly to one of the treatments. Assigning children randomly 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 treatments. In most clinical trials, we do 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. However, if one of the treatments is found to be better or safer than the others while the trial is still going on, the trial is stopped, and all children currently in the trial are given the treatment with the best results, when possible.

Participating in a clinical trial is 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 more information about clinical trials at www.childrensoncologygroup.org. You can discuss any questions with your treatment team.

Study Number

ACNS0831

Official Title

Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients with Newly Diagnosed Ependymoma Ages 1 to 21 years

Trial Opening Date

ACNS0831 opened on March 29, 2010. The ACNS0831 committee hopes to enroll 400 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 date to end.

General Patient Eligibility

• Age: 1-21 years
• Diagnosis: Newly diagnosed ependymoma located in the brain

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

General Background and Study Goal

Ependymoma is a rare childhood brain tumor. The outcome for children with this disease needs to be improved. The current standard of treatment for newly diagnosed ependymoma includes surgery to remove as much of the tumor as possible, followed by radiation therapy (the use of high-dose x-rays to kill cancer cells). It is unclear if adding chemotherapy to the standard treatment will improve survival. However, several previous studies have shown that chemotherapy might be helpful in the treatment of this disease.

The primary goal of this study is to determine if the addition of four cycles of maintenance chemotherapy after radiation improves the outcome of children with some kinds of ependymoma.

Other goals of the study are to:

• Examine if chemotherapy can improve outcomes for those children whose tumor is only partially removed during initial surgery.
• Study the effects of surgery, radiation therapy and chemotherapy on learning, thinking, hearing and the production of hormones (substances made in the brain that affect growth and development). This is an additional study, ALTE07C1.
• Study tumor tissue and blood for possible genetic and biologic factors related to ependymoma.

Summary of the Treatment

The treatment plan for all children includes initial surgery.

The study arm used following surgery will depend on three separate criteria:

1. How much of the tumor was removed
   1. If all of the tumor is removed it is called a gross total resection (GTR)
   2. If most of the tumor is removed it is called a near total resection (NTR)
   3. If some of the tumor remains it is called a sub total resection (STR)
2. Where the tumor is located
   1. Higher in the brain (supratentorial)
   2. Lower in the brain (infratentorial)
3. How the tumor looks under the microscope (called histology)
   1. Classic
   2. More aggressive (anaplastic)

Based on the information above, there are 3 arms on this study following initial surgery:

Arm 1: If the entire tumor was removed (GTR), and the tumor location was higher in the brain (supratentorial), and the tumor had classic histology

Treatment: Observation only (no further therapy)

Arm 2: If the tumor had anaplastic histology, or the tumor location was lower in the brain (infratentorial), or if most of the tumor was removed (NTR), patients will be randomly assigned to the following treatment:

Arm A: radiation therapy followed by observation

• radiation therapy lasts 6-7 weeks
• observation means no further treatment

Arm B: radiation therapy followed by chemotherapy

• radiation therapy lasts 6-7 weeks.
• maintenance chemotherapy consists of 4 cycles given over 12 weeks

Arm 3: If there was a sub total resection (some of the tumor remains)

Treatment:

Induction chemotherapy

• Induction therapy consists of 2 cycles of chemotherapy drugs given over 7 weeks.

Further therapy is based on how the tumor responded to the induction chemotherapy. Therapy following induction chemotherapy may include one or more of the following:

• Another surgical resection
• Radiation therapy
  • Radiation therapy will last 6-7 weeks
• Maintenance therapy or observation
  • Maintenance therapy consists of 4 cycles of chemotherapy given over 12 weeks.

If at any time during the study the tumor spreads to other areas of the brain or body, the patient will be taken off study therapy.

Special Considerations

• In order to learn more about ependymoma tumor cells, COG scientists will study some of the tumor taken out during surgery.
• Patients receiving chemotherapy will require additional hospitalizations and outpatient visits.
• Patients receiving radiation will require additional outpatient hospital days.

Risks and Side Effects

Chemotherapy and radiation can cause short and long-term side effects. 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. The study consent form has more details about possible side effects of the treatment in this study.

Contact Information

Your child’s oncologist and nurses are the best source for further information

Study Chairs

Amy A. Smith, MD
Arnold Palmer Hospital for Children

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