N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by New Approaches to Neuroblastoma Therapy Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New Approaches to Neuroblastoma Therapy Consortium
ClinicalTrials.gov Identifier:
NCT00885326
First received: April 18, 2009
Last updated: April 3, 2014
Last verified: April 2014

April 18, 2009
April 3, 2014
December 2009
December 2014   (final data collection date for primary outcome measure)
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.
  • Safety and feasibility [ Designated as safety issue: Yes ]
  • Toxicity as assessed by CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
  • Number of patients who are able to complete ≥ 4 courses with and without dose reductions and treatment delays [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00885326 on ClinicalTrials.gov Archive Site
  • 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.
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Development of bone events such as new metastases or fractures [ Designated as safety issue: No ]
Not Provided
Not Provided
 
N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma
A Phase I Study of Bevacizumab With Bolus and Metronomic Cyclophosphamide and Zoledronic Acid in Children With Recurrent or Refractory 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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Neuroblastoma
  • Drug: Bevacizumab
    Every course will be 28 days. Bevacizumab 10 mg/kg/dose , will be administered intravenously every 14 days beginning on day 0 of the second course.
    Other Names:
    • Avastin
    • BV
  • Drug: cyclophosphamide
    Cyclophosphamide will be administered as an intravenous (IV) bolus according to the protocol assigned dose level followed by daily oral dosing (25mg/m2/day) without interruption (unless toxicity supervenes).
    Other Names:
    • Cytoxan
    • CTX
  • Drug: zoledronic acid
    Administered on day 0 of course 1 and day 1 of course 2 and all subsequent courses in a dose of 4mg/m2 (max 4 mg per dose). On days when zoledronic acid (ZA) and cyclophosphamide (CTX) are given together, CTX should be given first.
    Other Names:
    • Zometa
    • ZA
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
December 2014
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be no more 30 years of age when enrolled on study.
  • Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
  • Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
  • Patients must have adequate heart, kidney, liver blood clotting and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
  • Patients must have recovered from all prior chemotherapy and surgical procedures

Exclusion Criteria:

  • They are known to be sensitive to Bevacizumab.
  • They have a history of very high blood pressure which required intensive intervention
  • They are pregnant or breastfeeding
  • Neuroblastoma is present in the brain on a CT or MRI scan done at study entry. Patients with neuroblastoma found in the bones of the skull are eligible if there is no tumor mass associated with them pressing on the brain.
  • They have a history non healing wounds
Both
up to 30 Years
No
Contact: Julia Glade-Bender, MD (212) 305-3379 jg589@columbia.edu
United States,   Canada
 
NCT00885326
CDR0000638257, P01CA081403, NANT2007-02
Yes
New Approaches to Neuroblastoma Therapy Consortium
New Approaches to Neuroblastoma Therapy Consortium
National Cancer Institute (NCI)
Principal Investigator: Julia L. Glade-Bender, MD Herbert Irving Comprehensive Cancer Center
New Approaches to Neuroblastoma Therapy Consortium
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP