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.