Introduction

This summary is intended to provide a general overview of the Children’s Oncology Group (COG) study ACNS0927. It tells who can be in this study and other basic information. The informed consent form has more details about the study. You can get this from your oncologist.

ACNS0927 is a therapeutic phase I/phase II trial. Therapeutic trials are research studies done to determine the safety and effectiveness of a treatment for a particular disease. Phase I trials are performed to learn the best dose of a chemotherapy drug, which is called the maximum tolerated dose or MTD. Phase II trials are performed to see if the MTD of a specific drug is effective or improves the survival rate of a particular disease.

Participating in a clinical trial is 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 more information about clinical trials at www.childrensoncologygroup.org. And be sure to discuss any questions with your treatment team.

Study Number

ACNS0927

Official Title

A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children with Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)

Trial Opening Date

ACNS0927 Part A opened to patient entry in August 2010. This portion of the study was completed in October 2011. Part B of this study opened to patient entry in February 2012. It is expected that Part B will remain open about 2 years.

General Patient Eligibility

• Age: 3 to 21 years
• Diagnosis: newly diagnosed diffuse intrinsic pontine gliomas (DIPGs) or brain stem tumors that are laboratory confirmed as anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma.

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

General Background and Study Goal

Diffuse intrinsic pontine gliomas (DIPGs) in children are very difficult to cure. A recent review of many clinical trials of pediatric diffuse brainstem tumors showed survival results of only 5-15% at 2 years. Radiation therapy can often cause a temporary response in both tumor size and symptoms in children with DIPG. Doctors hope that adding a drug that can increase the effect of radiation therapy (called a radio sensitizer) may potentially improve outcome.

Recent clinical studies have shown that a drug named Vorinostat (suberoylanilide hydroxamic acid or SAHA) both inhibits growth of malignant gliomas and enhances radiation sensitivity of these tumors.

The optimal dose of Vorinostat was determined in an earlier COG study, but doctors did not know if this dose would be tolerated if given along with daily radiation therapy. Part A of ACNS0927 studied various doses and schedules of Vorinostat to find the best dose when given along with radiation therapy. Part A of this study is now complete.

Part B of ACNS0927 will study whether giving an additional year of Vorinostat, after radiation is finished, will improve the survival rate of children with DIPG.

Summary of the Treatment

Part A:
Determined the best dose of Vorinostat; this portion is now complete.

Part B:
Chemoradiation phase: Vorinostat (in pill or liquid form) is taken Monday-Friday during radiation therapy. This phase usually lasts about 6 weeks.

Maintenance phase: Vorinostat (in pill or liquid form) is taken every day. A cycle of maintenance therapy is 28 days. Maintenance therapy may be continued for a maximum of 12 cycles.

Whenever possible these blood tests will be done when your child needs regular blood tests as part of transplant care.

Risks and Side Effects

Chemotherapy can cause short and long-term side effects. 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. The study consent form has more details about possible side effects of the treatment in this study

Special Considerations

• Children less than a certain weight (BMI < 1.25) will need to take Vorinostat in liquid form. This is because the pills come in only one strength, and this dose is too high for these children.
• Blood studies are needed weekly throughout this study.

Contact Information

Your child’s oncologist and nurses are the best sources for further information

Study Chair:
Jack Su M.D.
Texas Children's Cancer Center

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