Zoledronic Acid (ZOMETA) With Cyclophosphamide With Neuroblastoma and Cortical Bone Involvement

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.