A Phase I Study Of CEP-701 In Patients With Refractory Neuroblastoma (IND # 67,722)
- Determine the maximum tolerated dose of CEP-701 in pediatric patients with recurrent or
refractory high-risk neuroblastoma.
- Determine the dose-limiting toxicity of this drug in these patients.
- Determine the pharmacokinetic behavior of this drug in these patients.
- Determine the degree of TrkB tyrosine kinase inhibition activity present in the serum
of patients treated with this drug.
- Correlate the degree of TrkB tyrosine kinase inhibition activity in these patients with
dose level, pharmacokinetics, and antitumor activity data of this drug.
- Determine the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive oral CEP-701 twice daily* on days 1-5, 8-12, 15-19, and 22-26. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *On day 1 of course 1 only, patients receive oral CEP-701 once instead of twice.
Cohorts of 3-6 patients receive escalating doses of CEP-701 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Once the MTD is determined, the dose level is
expanded up to 9 patients.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD) of CEP-701 given on a twice daily chronic administration schedule (two days on , two days off) to children with high risk relapsed or residual neuroblastoma.
Within 28 days of treatment at each dose level.
John M. Maris, MD
Children's Hospital of Philadelphia
United States: Food and Drug Administration
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Children's Hospital and Regional Medical Center - Seattle||Seattle, Washington 98105|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Childrens Hospital Los Angeles||Los Angeles, California 90027|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus||Atlanta, Georgia 30322|
|University of Chicago Comer Children's Hospital||Chicago, Illinois 60637|
|Children's Hospital Boston||Boston, Massachusetts 02115|
|Lucille Salter Packer Children's Hospital, Stanford University||Palo Alto, California 94305|
|Morgan Stanley Children's Hospital of New York-Presbyterian||New York, New York 10032|