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

NEUROBLASTOMA Clinical Trial

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

Status Completed

Clinical Trial Summary

The purposes of this study are:

1. To find the highest dose of monthly intravenous Zometa that can be given with daily low doses of cyclophosphamide by mouth to children with recurrent or refractory neuroblastoma without causing severe side effects.

2. To find out the side effects seen by giving Zometa and cyclophosphamide on this schedule at different dose levels.

3. To measure blood and urine levels of Zometa during treatment

4. To preliminarily evaluate the antitumor activity of Zometa and concomitant oral cyclophosphamide in children with recurrent and/or refractory neuroblastoma within the confines of a Phase I study.

5. To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow

6. To measure the effects of Zometa on the immune system.

Clinical Trial Description

Zoledronic Acid (Zometa), a new generation, highly potent bisphosphonate used to treat osteoporosis and hypercalcemia of malignancy, is widely used in adult malignancies with potential for bone metastasis such as breast cancer, multiple myeloma and prostate cancer. Bisphosphonates modulate the bone environment by toxicity to osteoclasts resulting in decreased bone resorption. Zometa is the first bisphosphonate to affect both osteolytic and osteoblastic metastatic lesions. In several large randomized studies in adults with recurrent or advanced malignancies, patients randomized to Zometa had delay in progression of bone metastases and less morbidity (skeletal related events) when compared to either placebo or pamidronate. The toxicity profile of Zometa in adults has been tolerable and includes hypocalcemia, temperature rise, and nausea. The most concerning toxicity is decline in renal function that appears to be related to cumulative dose and the dose rate of administration. In our pre-clinical studies bisphosphonates delayed progression of osteolytic lesions in neuroblastoma tumors xenografted into immunocompromised mice while the combination of Zometa with low dose cyclophosphamide appeared to prolong overall survival. The primary aim of this study is to evaluate the maximum tolerated dose of Zometa combined with low dose oral cyclophosphamide in children with recurrent or refractory neuroblastoma. We will also evaluate the pharmacokinetics of Zometa in children with neuroblastoma and examine the effect of Zometa on markers of bone resorption, cytokines and bone-related growth factors. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• NEUROBLASTOMA

• NCT number: NCT00206388
• Study type: Interventional
• Source: Baylor College of Medicine
• Status: Completed
• Phase: Phase 1
• Start date: April 2005
• Completion date: May 2013