N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ 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.

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