Tolerability Study of Xerecept® in Pediatric Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Brain Edema, Brain Tumor

Intervention / Treatment
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* Drug: XERECEPT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) 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. Have one or more steroid-associated side effects at Screening (See Appendix A1 for a list of qualifying events) Capable of self-administration of subcutaneous injections twice daily or availability of assistance from caregiver. Karnofsky/Lansky performance status ≥ 40 Life expectancy of at least 6 months 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: Evidence of previous or current overt renal, hepatic or pulmonary diseases or active uncontrolled infection Subject and/or parent/guardian is unwilling or unable to comply with this protocol Subject has a known history of allergy or intolerance to hCRF or other ingredients in the Xerecept® solution (e.g., methionine, mannitol) Subject has a known history of hepatitis C virus, hepatitis B surface, or human immunodeficiency virus (HIV).

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xerecept<br>All patients will receive hCRF (XERECEPT) | Drug: XERECEPT<br>* BID dosing, subcutaneous for 1 year<br>* Other names: Corticorelin acetate injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | To define the maximum tolerated dose (MTD) of Xerecept® in pediatric patients; the MTD will be defined as the dose at which 1 or fewer of six patients experiences a dose limiting adverse event of any kind. | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dexamethasone Dosing | To explore if Xerecept®, when administered to pediatric patients, is effective in allowing decreases in dexamethasone dosing | 1 Year | 
| Incidence and severity of specified Steroid-Related Side Effects | To explore the clinical benefit associated with a reduction in steroid dosing over the course of the study by comparing the incidence and severity of pre-specified steroid-related side effects in all patients. | 1 year | 
| Number of patients with adverse events | Adverse events will be recorded at each study visit and detailed by SOC to define the safety profile of Xerecept in pediatric patients | 1 Year | 
| Change from baseline in clinical chemistry, hematology and urinalysis measures | Standard clinical chemistry, hematology and urinalysis measures will be analyzed at baseline and monthly during the study; changes from baseline will be measured over the course of the study | 1 Year | 
| PedsQL™ Quality of Life Inventory Scores | Child self report and parent proxy reports conducted at each study visit to assess changes in health-related quality of life over the course of the study | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peritumoral brain edema, edema, malignant brain tumor, brain tumor, dexamethasone, Decadron