N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zoledronic acid may stop the growth of tumor cells in bone. Giving bevacizumab together with cyclophosphamide and zoledronic acid may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects of giving bevacizumab together with cyclophosphamide and zoledronic acid in treating patients with recurrent or refractory high-risk neuroblastoma.
Drug: zoledronic acid
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Bevacizumab With Bolus and Metronomic Cyclophosphamide and Zoledronic Acid in Children With Recurrent or Refractory Neuroblastoma|
- Determination of toxicities and feasibility of the combination of bolus plus metronomic cyclophosphamide and zoledronic acid with and without bevacizumab when given to children with refractory or recurrent high risk neuroblastoma. [ Time Frame: Study entry, day 14 of course 1, prior to course 2, day 14 of course 2. ] [ Designated as safety issue: Yes ]Any dose limiting toxicity (DLT) as defined in section 9.2 of protocol.
- Evaluation of response within the confines of a phase I study. [ Time Frame: Before study treatment, prior to courses 3 and 6 and then after every 3rd subsequent course. ] [ Designated as safety issue: No ]Eligible patients are assessed for response after receiving 2 courses OR if they terminate treatment for reasons of toxicity OR if they progress prior to completion of 2 courses of therapy.
- Analysis of Circulating Endothelial Cells, Circulating Factors, Gene expression and Bone Metabolism Studies. [ Time Frame: Will be measured a total of 4 times, prior to start of course and then at day 14 of courses 1 and 2 only. ] [ Designated as safety issue: No ]Biologic studies will be done to analyse circulating endothelial cells(CEC), circulating precursor cells (CEP)and assessment of markers of bone metabolism.
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
- To determine the toxicities and feasibility of bolus and metronomic cyclophosphamide when given in combination with zoledronic acid with and without bevacizumab in patients with recurrent or refractory high-risk neuroblastoma.
- To preliminarily evaluate the antitumor activity of this regimen in these patients within the confines of a pilot study.
OUTLINE: This is a multicenter study.
Patients receive cyclophosphamide IV over 1 hour and zoledronic acid IV over 15 minutes on day 0 and oral cyclophosphamide once daily on days 1-27 in course 1. In course 2 and all subsequent courses, patients receive bevacizumab IV over 30-90 minutes on days 0 and 14, cyclophosphamide IV over 1 hour and zoledronic acid IV over 15 minutes on day 1, and oral cyclophosphamide once daily on days 0 and 2-27. Treatment repeats every 28 days for up to 2 years* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive up to 13 doses of zoledronic acid.
After completion of study treatment, patients are followed periodically.
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford University Medical Center|
|Palo Alto, California, United States, 94304|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94143|
|United States, Georgia|
|Children's Healthcare of Atlanta|
|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|
|C.S Mott Children's Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|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, Texas|
|Cook Children's Medical Center - Fort Worth|
|Fort Worth, Texas, United States, 76104|
|Texas Children's Cancer Center|
|Houston, Texas, United States, 77030-2399|
|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|
|CHU Sainte Justine|
|Montreal, Quebec, Canada, H3T 1C5|
|Principal Investigator:||Julia L. Glade-Bender, MD||Herbert Irving Comprehensive Cancer Center|