Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AEWS1031. It tells who is eligible and gives basic information about the study goals. More details about the study are in the consent form. You can get this from your oncologist.

AEWS1031 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 about treatment - its safety and how well it works. 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?

AEWS1031 compares two different treatments. These treatments are called study arms. Each treatment has been shown to be effective in other studies but these treatments have not been compared to each other. Usually, one study arm is the standard or the best proven current treatment. The other study arm has some changes and 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 participant is assigned to a study arm by a method called randomization. This is a process like flipping a coin that assures that each participant has a fair and equal chance of being assigned to any of the study arms. This makes sure the study arms can be compared fairly.

In most clinical trials, we will not know which treatment is better until everyone taking part in the trial has completed treatment and has 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 going on, the trial will be stopped. All participants 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

AEWS1031

Official Title

A Phase III Randomized Trial of Adding Vincristine-topotecan-cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-metastatic Ewing Sarcoma

Study Opening Date

AEWS1031 opened on 11/22/2010. The AEWS1031 committee hoped to enroll 640 patients, and has reached accrual goals.

General Patient Eligibility

• Age: 50 years of age or younger
• Diagnosis: Newly diagnosed Ewing Sarcoma or Peripheral Neuroectodermal Tumor (PNET) of bone or soft tissue.
• Patients with disease that is spread from the initial site of disease are NOT eligible for this study

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

General Background and Study Goal

Ewing Sarcoma is a malignant tumor that develops in the bone or soft tissue. The current best treatment for Ewing sarcoma that has not spread from the primary site is an initial 12 week course of chemotherapy followed either by surgical removal of the tumor or radiation aimed directly at the tumor. In some cases, both surgery and radiation are used. Following surgery and/or radiation, chemotherapy is continued for approximately 6 months. For some patients, radiation and chemotherapy may be given simultaneously.

Topotecan is a drug that has been used for many pediatric cancers including Ewing sarcoma. Topotecan has been useful in treating people with Ewing sarcoma that has recurred (returned after treatment). Doctors hope to learn if the addition of topotecan to standard chemotherapy will improve outcomes for patients with newly diagnosed Ewing sarcoma. It is not known if adding topotecan will increase the side effects of treatment. In other studies in children with Ewing sarcoma it has been tolerated well.

The study goal is to determine if the addition of topotecan can improve the overall survival for children, adolescents and young adult participants with Ewing sarcoma without adding unacceptable side effects.

Summary of the Treatment

One group of patients will receive standard chemotherapy (Regimen A). The other group will receive the standard chemotherapy medications with the addition of topotecan (Regimen B).

Regimen A: Standard treatment includes the chemotherapy drugs Vincristine, Doxorubicin, Cytoxan, Ifosfamide and Etoposide.

• Cycles repeat every 14 days, for a total of 17 cycles.

Regimen B: Standard treatment & Topotecan includes the chemotherapy drugs Vincristine, Doxorubicin, Cytoxan, Ifosfamide, Etoposide with Topotecan added.

• Cycles repeat every 14 days for a total of 17 cycles.

Treatment is divided into 3 phases:

• Induction - 6 cycles of chemotherapy
• Local control – surgery to remove the tumor, and/or radiation therapy if the tumor is not in an area where it can be safely removed
• Consolidation - 11 cycles of chemotherapy

Special Considerations

Patients treated on Regimen B will have more hospital/infusion visits, during the 5 cycles that Topotecan is given, as Topotecan is administered over 5 days.

Risks and Side Effects

Radiation and 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

Patrick J. Leavey MD
University of Texas Southwestern Medical Center

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

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS