Protocol

PBTC33: A Phase I /II Study of ABT-888, an Oral Poly (ADP-Ribose) Polymerase Inhibitor, and Concurrent Radiation Therapy, followed by ABT-888 and Temozolomide (TMZ), in Children with Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)

Diseases

Brain Tumor : newly diagnosed diffuse intrinsic pontine gliomas (DIPG)

Description

Diffuse Intrinsic pontine gliomas are located in the brainstem, at the base of the brain. They are usually diagnosed in children aged 5 to 10 years. They are difficult to treat because the tumor cells grow in between and around normal cells. These tumors are generally treated with radiation therapy, which is a combination of high-energy X-rays that destroy tumor cells. This treatment can reduce symptoms significantly, but even with radiation therapy, the cure rate is still very low for these tumors. New drugs such as ABT-888 are being investigated to assist with the search for treatments that can improve survival in these patients.

The phase I portion of this study will help to find out the highest safe dose of ABT-888 that can be given with radiation therapy to treat children with DIPG. While doctors know the safe dose of ABT-888 and TMZ when given together, they do not yet know the safe dose of ABT-888 when it is given at the same time as radiation treatment. The phase II portion of this study will help to find out the efficacy of this treatment in patients with DIPG.

Objectives

• To find the highest dose of ABT-888 that can be safely given at the same time as radiation therapy. This is the dose that will be used later in phase II of this study.
• To estimate the overall survival of children with DIPG in phase II of this study
• To learn what side effects may occur when ABT-888 is given with radiation followed by maintenance therapy with ABT-888 and temozolomide (TMZ).
• To learn how children’s bodies process ABT-888 when given during radiation by studying the levels of ABT-888 in the blood (PK study).
• To see if it is safe to increase the dose of TMZ during maintenance therapy dose.
• To learn from cells in your blood whether ABT-888 is effective in shutting down the PARP protein and preventing the repair of damaged DNA after radiation.
• To study the PARP activity and DNA repair protein levels in tumor samples from children with atypical pontine gliomas that are enrolled on this study (if leftover tumor specimens are available from past surgeries or biopsies).
• To learn if different types of MRI studies can help us tell the difference between pseudo-progression (sometimes DIPG tumors look bigger on MRI scan after radiation, but will get smaller after a few weeks) and true early progression of a tumor.
• To learn if certain substances in urine can help us identify both disease progression and response of DIPG to ABT-888, radiation and TMZ treatment.

Eligibility

• Patient should be less than or equal to 21 years of age at registration
• Patient must be able to swallow oral medications
• Patients must have not received any prior therapy other than surgery and/or steroids
• Female patients of childbearing potential must not be pregnant or breastfeeding
• Patient does not have seizures or history of seizures.

Contact

Ibrahim Qaddoumi MD
St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105 USA
Phone: 901-595-2544 or 901-595-4599
FAX: 901-595-5353

Or

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
Phone: 901-595-2544

For the current eligibility status of this clinical study, patient’s family, relatives and/or referring physicians may contact St. Jude Children’s Research Hospital at (901) 595-4599 or (901) 595-2544.

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.