N2001-03: CEP-701 in Treating Young Patients With Recurrent or Refractory High-Risk Neuroblastoma
RATIONALE: CEP-701 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
PURPOSE: This phase I trial is studying the side effects and best dose of CEP-701 in treating young patients with recurrent or refractory high-risk neuroblastoma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Of CEP-701 In Patients With Refractory Neuroblastoma (IND # 67,722)|
- 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. [ Time Frame: Within 28 days of treatment at each dose level. ] [ Designated as safety issue: Yes ]
- To determine dose limiting toxicities (DLTs) of CEP-701 given on this schedule [ Time Frame: Within first 28 days of therapy. ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetic (PK) behavior of CEP-701 in children with residual or refractory high-risk neuroblastoma. [ Time Frame: Days 1,5 and 26 of first course only. ] [ Designated as safety issue: Yes ]Participation in PK studies is voluntary and not a requirement for study entry.
- To determine the degree of TrkB tyrosine kinase inhibition activity present in the serum of patients treated with CEP-701, and correlate these findings with dose level, pharmacokinetic and anti-tumor activity data. [ Time Frame: Days 1,5 and 26 of first course only. ] [ Designated as safety issue: No ]
- To define the antitumor activity of CEP-701, within the confines of a Phase I study. [ Time Frame: Evaluation at end of courses 1, 2, 4 and then every 4 courses until patient goes off therapy. ] [ Designated as safety issue: No ]
|Study Start Date:||August 2003|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
- 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.
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucille Salter Packer Children's Hospital, Stanford University|
|Palo Alto, California, United States, 94305|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94143|
|United States, Georgia|
|AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comer Children's Hospital|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|Morgan Stanley Children's Hospital of New York-Presbyterian|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104-4318|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Principal Investigator:||John M. Maris, MD||Children's Hospital of Philadelphia|
|Study Chair:||Garrett M. Brodeur, MD||Children's Hospital of Philadelphia|