Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AOST1421. 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.

AOST1421 is a Phase 2 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 2 trial is to learn if a new treatment works in treating a specific type of cancer and how it affects the body.

In a Phase 2 trial, patients with a specific type of cancer receive a new treatment using a dose that was found to be safe in a Phase I trial. Patients are checked for side effects of the treatment and to see whether the cancer shrinks or goes away.

Phase 2 trials are offered to patients whose disease has not responded to standard types of treatments or to patients whose disease doesn't have a standard treatment.

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

AOST1421

Study Title

A Phase 2 Study of Human-Mouse Chimeric Anti-Disaloganglioside Monoclonal Antibody ch14.18 in Combination with Sargramostim (GM-CSF) in Patients with Recurrent Osteosarcoma

Study Opening and Closing Date

AOST1421 opened on 11/30/2015 and closed to patient accrual on 8/17/2018.

General Patient Eligibility

• Age: less than 30 years
• Diagnosis: Osteosarcoma that has returned only in the lungs
• All sites of cancer in the lung must be surgically removed within 4 weeks prior to study enrollment
• Patients with the following are not eligible: osteosarcoma that has returned in the bone or other sites outside the lung

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

General Background and Study Goal

While the introduction of standard chemotherapy has improved survival rates in patients with localized osteosarcoma, patients with osteosarcoma that comes back (recurs) after treatment is complete have poor outcomes. New ways of treating recurrent osteosarcoma are needed.

GD2 is a protein that is important for cancer cell growth, and is found in many tumors including osteosarcoma. Ch14.18 (dinutuximab) is an antibody against the GD2 protein that has shown activity in a variety of cancers including osteosarcoma, both in laboratory studies and clinical trials. Ch14.18 "turns off" the effects of GD2 on cancer cells and stimulates the body's immune system to stop cancer cells from growing. Recent studies in other childhood cancers that depend on GD2 to grow have shown that ch14.18 has been effective in stopping cancer growth, and may be even more effective when given with other agents that stimulate the immune system like GM-CSF.

Ch14.18 has been safely used to treat children with different types of cancer, including some with osteosarcoma.

The goal of this study is to see how well ch14.18 and GM-CSF in combination work to prevent recurrent osteosarcoma from returning to the lungs.

Summary of the Treatment

• All patients on the study will receive the same treatment.
• GM-CSF is given as a subcutaneous (into the fat layer under skin) injection daily for 14 days. The injections will start 3 days before ch14.18 antibody begins, and will usually begin on a Friday. You or a family member will be taught how to give this injection. Start date of GM-CSF is considered cycle day 1.
• Ch14.18 infusion will be given daily for 2 days on day 4 & 5 of each cycle
• Ch14.18 infusion lasts 20 hours and is given in the hospital
• Each cycle consists of 28 days
• The study continues for a total of 5 cycles

Temporarily closed to accrual on 1/23/2018 pending evaluation of patients currently enrolled on the study.

Stratum 1 was closed to accrual on 6/27/2016 as patient accrual goals were met.

Special Considerations

• Ch14.18 antibody may cause infusion reaction and pain associated with medication administration. If this happens, the ch14.18 infusion may need to be interrupted, or slowed down. Additional days (up to 2) may be needed to complete the entire dose.
• Pain medications and medications to help reduce the chance of an allergic reaction will be given before each day's infusion of ch14.18.
• Participating patients of reproductive age who are sexually active must agree to use an effective method of contraception throughout the study and continue this until 2 months after the last dose of ch14.18.

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 Chairs

Pooja Hingorani, MD
Phoenix Children’s Hospital

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS