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.

Study Overview

• Status: Terminated
• Conditions: Brain Tumor; Brain Edema
• Intervention / Treatment: Drug: XERECEPT

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital, Northwestern University Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute Pediatric Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Xerecept; All patients will receive hCRF (XERECEPT)	Drug: XERECEPT; BID dosing, subcutaneous for 1 year; Other Names: hCRF; Corticorelin acetate injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celtic Pharma Development Services

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: June 7, 2011
• First Submitted That Met QC Criteria: June 7, 2011
• First Posted (ESTIMATE): June 8, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 29, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: edema; brain tumor; dexamethasone; Decadron; malignant brain tumor; peritumoral brain edema
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms; Brain Edema; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Corticotropin-Releasing Hormone
• Other Study ID Numbers: CPDS 1001