Tolerability Study of Xerecept® in Pediatric Patients

A Phase I/II Open Label Individual Dose Titration Trial of the Human Corticotropin- Releasing Factor (hCRF), Corticorelin Acetate Injection (Xerecept®), to Determine the Tolerability of Xerecept® in a Pediatric Population

This study is being conducted to evaluate the safety and tolerability of Xerecept® in children with central nervous system tumors and to identify appropriate doses of Xerecept® to be used in subsequent pediatric clinical trials.

Steroid-related side effects are much more severe in a pediatric population than they are in adults. The side effects appear more quickly and are often apparent in as few as 14 days. Dexamethasone side effects in children include rounding of the face, acne, increased body hair, muscle weakness, osteoporosis, mood changes, weight gain, fluid retention, glucose instability, high blood pressure, increased susceptibility to infection, stunted growth and aseptic necrosis of the hip joints14-16.

Although extensive studies have been performed with Xerecept® in adults, no studies have been performed with Xerecept® in pediatric subjects. Therefore, this study is being conducted to evaluate the safety and tolerability of Xerecept® in children with central nervous system tumors and to identify appropriate doses of Xerecept® to be used in subsequent pediatric clinical trials. The study will also explore if Xerecept®, when administered to pediatric patients, is effective in allowing decreases in dexamethasone dosing

Inclusion Criteria:

1. Have histologically confirmed primary, recurrent or metastatic cerebral tumors and require chronic steroid dosing to manage symptoms of peritumoral brain edema (No histological confirmation is required of optic pathway tumors or brain stem gliomas)
2. Have been taking dexamethasone (or equivalent) at a dose of ≥1 mg/day for a minimum of 14 days and have had a stable dose for at least 7 days.
3. Have one or more steroid-associated side effects at Screening (See Appendix A1 for a list of qualifying events)
4. Capable of self-administration of subcutaneous injections twice daily or availability of assistance from caregiver.
5. Karnofsky/Lansky performance status ≥ 40
6. Life expectancy of at least 6 months
7. Female subjects must not be pregnant or breast-feeding and, if of childbearing potential, must use adequate methods of contraception during the study

10. Ability to provide written informed consent or, if unable to provide, have a legal guardian or representative provide written informed

Exclusion Criteria:

1. Evidence of previous or current overt renal, hepatic or pulmonary diseases or active uncontrolled infection
2. Subject and/or parent/guardian is unwilling or unable to comply with this protocol
3. Subject has a known history of allergy or intolerance to hCRF or other ingredients in the Xerecept® solution (e.g., methionine, mannitol)
4. Subject has a known history of hepatitis C virus, hepatitis B surface, or human immunodeficiency virus (HIV).