INTRODUCTION

This family protocol summary is about the Children's Oncology Group study AEWS1221. It tells who is eligible and gives basic information about the study. More details about the study are in the consent form. You can get this from your oncologist.

AEWS1221 is a Phase 3 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 3 trial is to learn if a drug or 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?

AEWS1221 compares two different treatments. 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 than the standard treatment.

In a Phase 3 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. This 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 getting checked 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 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 out more information about clinical trials at www.childrensoncologygroup.org. Always discuss any questions that you may have with your treatment team.

STUDY NUMBER

AEWS1221

OFFICIAL TITLE

Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab to Multi-agent Chemotherapy for Patients with Newly Diagnosed Metastatic Ewing Sarcoma

STUDY OPENING

AEWS1221 opened on 12/8/14. The AEWS1221 committee hopes to enroll 300 patients.

GENERAL PATIENT ELIGIBILITY

• Age: 50 years of age or younger
• Diagnosis: Newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue who also have disease involving lung, bone, bone marrow, or other sites
• Patients with primary tumors in the brain or spinal cord are not eligible for the study
• Patients with diabetes mellitus will be excluded from the study

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

GENERAL BACKGROUND AND STUDY GOAL

There has been considerable improvement in the outcome of patients with localized Ewing sarcoma over the last two decades. Unfortunately, patients diagnosed with Ewing sarcoma that has spread to other areas of the body continue to have poor outcomes when treated with standard chemotherapy. Ganitumab is a new agent which has shown activity against Ewing sarcoma in both laboratory studies and prior clinical trials. Ganitumab is part of a class of drugs called insulin growth factor receptor-1 monoclonal antibodies (IGF-1R antibodies). IGF-1R is a molecule that can be found on cancer cells and promote cancer growth. Ganitumab is designed to block the function of IGF-1R in cancer cells and stop cancer growth. Recent studies have shown that Ganitumab has activity against Ewing sarcoma cells when used alone, and may increase the effectiveness of other chemotherapy agents with given in combination with other agents. Doctors hope to learn if the addition of Ganitumab to standard chemotherapy will improve outcomes for patients with metastatic Ewing sarcoma. It is not known if adding Ganitumab will increase the side effects of treatment.

SUMMARY OF THE TREATMENT

At study entry, patients will be randomized to either

• Regimen A (standard chemotherapy)
• Regimen B (standard chemotherapy + Ganitumab)

Treatment will consist of 5 phases of therapy: induction; local control; consolidation; metastatic site irradiation; and maintenance. Maintenance will only be administered to patients on Regimen B.

Induction (12 week): All patients receive 6 cycles of chemotherapy administered every 14 days (standard treatment). Patients on regimen B will receive Ganitumab on day 1 of each chemotherapy cycle.

Local control: Local control for all patients will take place once patients recover from induction chemotherapy (approximately week 13). Local control may consist of surgery, radiation, or a combination of both to address the primary tumor. For patients receiving radiation alone, consolidation therapy should begin at the same time as radiation.

Consolidation (16 weeks): All patients will receive 8 cycles of chemotherapy administered every 14 days (standard treatment). Patients on regimen B will receive Ganitumab on day 1 of each chemotherapy cycle in cycles 4 to 8 only.

Metastatic site radiation: All patients will receive. Radiation begins once the patient has recovered from the last cycle of consolidation. No Ganitumab or chemotherapy will be given during radiation.

Maintenance (24 weeks): Only patients on regimen B will receive maintenance therapy with Ganitumab every 3 weeks for 8 doses.

SPECIAL CONSIDERATIONS

• If scheduled chemotherapy is delayed, the patient will be required to obtain labs on the day chemotherapy was scheduled to be administered. This blood may be drawn from a central line.
• Ganitumab will be provided free of charge and supplied by National Cancer Institute (NCI).

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 and nurses are the best sources for further information.

STUDY CHAIR

Steven DuBois, MD, MS
UCSF Benioff Children's Hospital

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS