Introduction

This family protocol summary provides a general overview of the Children's Oncology Group (COG) study AOST1521. 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.

AOST1521 is a Phase II 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 a 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 1 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

AOST1521

Study Title

A Phase 2 Study of GPNMB-targeted Antibody-Drug Conjugate, CDX-011 (Glembatumumab Vedotin), in Recurrent or Refractory Osteosarcoma

Study Opening/Closing Date

AOST1521 opened on 2/16/2016 and closed to patient enrollment as of 2/3/17.

General Patient Eligibility

• Age: 12-50 years of age
• Diagnosis: Osteosarcoma that has returned after treatment (recurrent) or has stopped responding to standard treatment (refractory)

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

General Background and Study Goal

Patients who have osteosarcoma that no longer responds to treatment or comes back after treatment have a poor outcome with current best available treatment. New ways of treating refractory or recurrent osteosarcoma are needed.

CDX-011 (glembatumumab vedotin) is a drug that provides a new approach to treating cancer cells. CDX-011 is an antibody (type of protein) attached to a chemotherapy drug called MMAE. Glycoprotein non-metastatic B (GPNMB) is a protein that is found on the inside of some types of normal cells and can be found attached to the outside, or acting abnormally, in osteosarcoma cells.

The antibody part of CDX-011 helps attach the chemotherapy drug part to the GPNMB protein found on osteosarcoma cells so that the MMAE chemotherapy can kill the cells.

The goal of this study is to demonstrate whether CDX-011 therapy can stop tumor growth or shrink tumors within the first several months of starting treatment. In addition, the study will identify side effects associated with CDX-011 therapy in patients with osteosarcoma.

Summary of the Treatment

• CDX-011 will be given by IV (intravenously) over 90 minutes every 21 days. Each 21-day period is called one cycle
• The study may continue for up to 14 months or 18 cycles
• Patients will be evaluated for disease response after cycles 2, 4 and 6, and then after every 3rd cycle
• Patients who achieve a partial response (tumor shrinkage) after Cycle 2 that is confirmed after Cycle 6 may undergo resection (surgical removal) or radiation of sites of disease if recommended by their doctor
  • CDX-011 therapy will be stopped for surgery and will start again at least 2 weeks after surgery.
  • CDX-011 therapy will be stopped during radiation, and can start again once radiation is complete.
• Treatment will be stopped if there is evidence of tumor growth or severe toxic side effects related to the drug

Special Considerations

• A number of food, drug, and supplement interactions can occur with CDX-011. Please review your current medication list, including supplements, with your oncologist.
• To enter the trial, patients must have disease that can be measured for size on scans.
• Samples of the patient's tumor must be available to be sent to a lab to see if the tumor expresses GPNMB
• Patients with nerve problems that interfere with their ability to walk without assistance or perform every day activities such as buttoning a shirt, writing, or using utensils, will not be able to participate
• Patients with tumors in the central nervous system will not be able to participate
• The first six patients who are age 14 or younger will have additional blood samples drawn with the first cycle. These are required to participate in the study. These blood samples are optional for patients aged 15 to 21.
• CDX-011 may be harmful to a developing baby.
  • Patients of reproductive age who are sexually active must agree to use a highly effective contraceptive method during the study and for 2 months after the end of study treatment.
  • Women of childbearing age must have a negative pregnancy test prior to starting therapy.
  • Women who are pregnant cannot participate in the study.
  • Breastfeeding women are not eligible unless they have agreed not to breastfeed their infants.

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 you or 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 or your child's oncologist and nurses are the best sources for further information.

Study Chair

Lisa M. Kopp, DO
The University of Arizona Medical Center
Tucson, Arizona

FAMILY PROTOCOL SUMMARY REVIEW/APPROVALS