Introduction

This family protocol summary provides a general overview of the Children’s Oncology Group (COG) study ACNS0334. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form and protocol.  You can get these from your oncologist.

ACNS0334 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?

ACNS0334 compares 2 treatments. These treatments are called study arms.  Usually, one study arm is the standard or the best proven current treatment. The other study arm has 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 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 better 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

ACNS0334

Official Title

A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children < 36 Months Old with Intensive Induction Chemotherapy with Methotrexate Followed by Consolidation with Stem Cell Rescue versus the Same Therapy without Methotrexate

Trial Opening Date

ACNS0334 opened on August 6, 2007. The ACNS0334 committee hopes to enroll 100 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 enrollment.

General Patient Eligibility

•    Age: birth to 36 months
•    Diagnosis: high risk medulloblastoma or primitive neuroectodermal tumor (PNET)
•    No prior radiation therapy or chemotherapy

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

General Background and Study Goal

There is currently no standard treatment for young children with high risk medulloblastoma/PNET. Several research studies have treated children with these diagnoses with intense chemotherapy and stem cell rescue.

In a previous clinical trial a chemotherapy drug called Methotrexate was added to a 4-drug chemotherapy regimen that had been used in several earlier trials. This was followed by intense chemotherapy with stem cell rescue. In children with tumors that had spread, high rates of complete disappearance of the tumor were seen.

The purpose of this study is to compare 2 treatment arms to see if one is better for young children with medulloblastoma/PNET. Each arm consists of intense induction chemotherapy followed by consolidation chemotherapy and stem cell rescue. The difference between the arms is that an additional drug, Methotrexate, is added during the induction phase in arm B, and is not added in arm A. 

The overall goal of this study is to compare the effects of therapy that includes Methotrexate with therapy that does not include Methotrexate in children less than 3 years of age with high risk medulloblastoma/PNET to find out which is better.

Other goals of this study are to:
•    see how the study treatments affect quality of life
•    see how the study treatments affect brain development
•    look at samples of tumor tissue to see if there are differences in tumors that can help scientists learn more about high risk medulloblastoma/PNET and ways to treat it

Summary of the Treatment

Patients will receive one of two treatment arms. All patients will receive induction chemotherapy, consolidation chemotherapy and stem cell rescue. The difference between the 2 arms occurs only during the Induction phase of treatment. Patients randomized to arm B will have the chemotherapy drug, Methotrexate, added to the Induction phase. The treatment for both regimens is the same during Consolidation and stem cell rescue.

Treatment on this study takes about 6 months. Patients will receive a total of 6 cycles of chemotherapy. They will receive 3 cycles during Induction therapy and 3 cycles during Consolidation therapy. Each cycle of Induction chemotherapy lasts about 21 days and Consolidation chemotherapy about 28 days. During each cycle of Consolidation some of the patient’s own stem cells will be given to them to help their bone marrow recover more quickly.

If the tumor goes away after the Induction therapy, the patient will go on to Consolidation therapy. If the tumor has gotten smaller but is not completely gone or does not change in size after Induction therapy, the patient may have a second surgery to try to remove the rest of the tumor before going on to Consolidation therapy.

During the study, if the tumor gets larger, the patient will be taken off study therapy and other treatment options will be discussed with your child’s doctor.

Special Considerations

If a patient takes part in this study, specialists from COG will study:
•    tumor tissue that was removed at the time of diagnosis and from a second surgery, if one is done
•    copies of the MR scans used to make the diagnosis of medulloblastoma/PNET and those MRI done to evaluate the tumor during and after treatment
•    additional testing performed in a COG-approved laboratory on the tumor tissue and a small blood sample obtained before beginning treatment

•    Patients who are randomized to receive Methotrexate (Arm B) will have a longer stay in the hospital during Induction chemotherapy cycles than those who do not receive on Arm A. 
•    Consolidation therapy must occur at a COG-accredited transplant program

Risks and Side Effects

Chemotherapy 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 is the best source for further information. 


Study Co-Chairs:
Claire Mazewski, MD                Stewart Kellie, MBBS MD
Children’s Healthcare of Atlanta        The Children’s Hospital of Westmead
Emory University

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