Clinical Trials

Study : NANT 2004-01

Zometa and Cyclophosphamide in Resistant Neuroblastoma Patients with Bone Disease

Protocol Title: A Phase I Study of Zoledronic Acid (Zometa) with Cyclophosphamide in Children with Recurrent/Refractory Neuroblastoma and Cortical Bone Involvement

Study Chair: Heidi Russell, MD.(Texas Children's Hospital, Baylor College of Medicine)

What is this study about:

Reseachers are exploring new ways of treating neuroblastoma that no longer responds to standard treatments. One potential new way to treat tumors is to change the normal cells around the tumor, making it more difficult for tumors to grow. Zometa is a drug that works against a type of cell in the bone called osteoclasts. Osteoclasts are important for neuroblastoma tumor cells to spread to the bone and form painful tumors there. When researchers used Zometa with cyclophosphamide in laboratory experiments to treat neuroblastoma in animals, they found that the combination slowed the growth of tumors in bones and other places as well. Therefore investigators have put the two drugs, Zometa and cyclophosphamide, together for this study. This is the first clinical trial to test these drugs together in children. Zometa has been used before in adults to help decrease bone fractures and damage caused by cancer cells, but this is the first time it will be used in a clinical trial in children. Cyclophosphamide is a standard chemotherapy drug that is used to treat neuroblastoma. This clinical trial will help find the highest Zometa dose that can be safely given together with cyclophosphamide to patients with resistant neuroblastoma that have bone disease.

Why is this study being done:

• To find the highest dose of Zometa that can be given with the same dose of cyclophosphamide without causing bad side effects. This is done by increasing the dose of Zometa in one group of patients at a time, until we find the highest dose that can be given without bad side effects.
• To find out the side effects seen by giving this drug combination on this schedule.
• To measure blood and urine levels of Zometa during treatment.
• To determine if your tumor gets smaller after treatment with Zometa and cyclophosphamide.
• To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow.
• To measure the effects of Zometa on the immune system.

Criteria which need to be met to participate in this study:

• Patients must have been no more than 30 years of age when enrolled on the study.
• Patients must have neuroblastoma and bone disease that fits into one of three options:

  A.  Patients must have relapsed neuroblastoma and bone disease that can be seen either on MIBG scan or bone scan or x-ray. OR

  B.  Patients must have refractory neuroblastoma with less than a partial response to standard treatment and bone disease that can be seen either on MIBG scan or boone scan or x-ray OR

  C.  patients must have persistent disease after at least a partial response to standard treatment and bone disease that can be seen either on MIBG scan or bone scan or x-ray. Patients in this category will need to have a biopsy done of one of the sites of disease that is left to show that it is neuroblastoma in order to enroll in the study.

• Patients must have adequate kidney, liver and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
• Patients must have a stable blood calcium level. Patients can be on calcium supplements.

Patients cannot participate in the study if:

• They have been treated before with Zometa or other drugs that are like it (known as bisphosphanates).
• If they take another investigational medicine while they are on this study.
• They are pregnant or breast feeding.
• They have an uncontrolled infection.
• They have had an allogeneic stem cell transplant in the past (using stem cells from a donor other than yourself).
• They think they might not be able to cooperate with the required visits and tests to monitor for safety while on this study.

Study procedures:

Zometa is given by IV and cyclophosphamide is given by mouth. One "course" of treatment is 28 days. You may continue with this treatment for as long as your doctor feels it is helping you and it is not causing severe side effects.

Cyclophosphamide will be taken by mouth once a day, every day.
It will either be a liquid or a pill, depending on your weight and if you can take pills. It is important to take this drug in the morning and to try to drink fluids all day long.

Zometa is given by IV once a month over 15 minutes.

You will also be asked to take calcium and Vitamin D to reduce the chances that you will have some side effects because of the Zometa. All patients will take at least one dose of these medicines each day, some patients may need to take more.

The table shows when Zometa ( Z ) and cyclophosphamide ( C ) and calcium and vitamin D will be given:

If you would like to download or print a sample consent form for this clinical trial, please click here : N04-01consentver2-14-05.pdf

If you would like to download this page in Microsoft Word format, please click here : N2004-01

[ If you are interested in getting more information about this clinical trial, please click here to send us an email. ]