A Phase I Study of Zoledronic Acid (Zometa) With Cyclophosphamide in Children With Recurrent or Refractory Neuroblastoma and Cortical Bone Involvement (NANT 2004-01)

Inclusion Criteria:

- Less than or equal to 30 years of age when enrolled on study.

- A diagnosis of neuroblastoma either by histologic verification of neuroblastoma
and/or demonstration of tumor cells in the bone marrow with increased urinary
catecholamines.

- High-risk neuroblastoma with at least ONE of the following: 1. Recurrent/progressive
disease. 2. Refractory disease (i.e. less than a partial response to frontline
therapy). No biopsy is required for eligibility for study. 3. Persistent disease
after at least a partial response to frontline therapy (i.e. patient has had at least
a partial response to frontline therapy but still has residual disease by MIBG,
CT/MRI, or bone marrow). Patients in this category are REQUIRED to have a biopsy of
at least one residual site demonstrating viable neuroblastoma.

- Bone disease demonstrated by uptake on MIBG scan. If the patient's tumor is known to
be non-avid for MIBG then the patient must have evidence of either new lesions or
progression of prior lesions on bone scan or plain radiographs.

- A Karnofsky or Lansky performance status of greater than or equal to 50%. Patients
who are unable to walk because of paralysis or tumor pain, but who are up in a
wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.

- Life expectancy of greater than 2 months.

- Fully recovered from the acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study. 1. Must not have
received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea). 2.
Patients must not have received radiation for a minimum of four weeks prior to study
entry at the site of any lesion that was biopsied to document study eligibility. A
minimum of six weeks is required following prior large field radiation therapy (ie:
TBI, craniospinal therapy, whole abdomen, total lung, or over 50% marrow space). 3.
Patients must not have had an autologous stem cell transplant within 3 months of
entry onto this study. Patients status post-allogeneic stem cell transplant are
excluded. 4. A minimum of six weeks is required following prior therapeutic doses of
MIBG. 5. Must not have received factors that support platelet or white cell number or
function within 7 days of study entry. 6 Must not have received bisphosphonate
therapy.

- Must not be receiving any other anti-cancer agents or radiotherapy at the time of
study entry or while on study.

- Organ Function Requirements Adequate Bone Marrow Function: a. ANC greater than or
equal to 750 b. Platelet count greater than or equal to 50,000, transfusion
independent (defined as no platelet transfusion for one week). NOTE: hematologic
criteria must be met by all patients, regardless of neuroblastoma involvement in bone
marrow. Adequate Renal Function a. Glomerular Filtration Rate of greater than or
equal to 70 ml/min/1.73 m2, OR b. Age-adjusted normal serum creatinine for age
Adequate Liver Function a. Total bilirubin less than or equal to 1.5 x normal for
age, and b. SGPT (ALT) and SGOT (AST) less than 5 x normal for age.

- Ionized serum calcium greater than or equal to 1.0 mmol/L (Patients are allowed to be
on calcium supplements if serum calcium is stable)

- Urinalysis with less than or equal to 1+ heme.

- Reproductive Function: Negative serum beta-HCG in females and use of effective
contraception in females and males of child-bearing potential.

Exclusion Criteria:

- Status post-ALLOGENEIC stem cell transplant.

- Received prior bisphosphonate therapy.

- Receiving other investigational agents.

- Have an uncontrolled infection.

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.

- Pregnancy or breast feeding.