Clinical Trials

Study : NANT 2007-02

Protocol Title: A Phase I Study Of Bevacizumab With Bolus And Metronomic Cyclophosphamide And Zoledronic Acid In Children With Recurrent Or Refractory Neuroblastoma

Study Chair: Julia Glade-Bender, MD. (Morgan Stanley Children's Hospital of New York Presbyterian)

What is this study about?

This clinical trial is combining three agents, each that have been tried in recurrent neuroblastoma before.

Cyclophosphamide is a well known chemotherapy drug used to treat neuroblastoma. Usually it has been given as a high dose into a vein (intravenous or IV). This method tends to kill a large number of cells at one time, but can only be given every few weeks. During the breaks between doses there is a risk that the tumor may start to grow again. Another way to give cyclophosphamide is to give it orally every day, a method called metronomic dosing. It is felt to affect the tumor as well as the blood vessels that feed the tumor. This method has been easy for patients to tolerate. However, giving both IV and orally together has not been done.

One potential new way to treat tumors is to change the normal cells around the tumor, making it more difficult for tumors to survive. 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. Bevacizumab is a drug that works against how blood vessels grow and are brought to the tumor. All tumors require blood vessels to survive.

When investigators put these drugs together in experiments to treat neuroblastoma in animals, they found that the combination slowed the growth of neuroblastoma tumors. The combination of oral metronomic cyclophosphamide and Zometa has been studied in children with neuroblastoma in a phase I study, a study to find out a safe dose of Zometa, and found that the combination was tolerated well, and some children's tumors responded. Bevacizumab has also been studied in a phase I study in children. This clinical trial will combine these different drugs to study if they can safely be given together to patients with recurrent or resistant neuroblastoma.

The purposes of this study are:

To find out if it is feasible to give a combination of intravenous (IV) and oral cyclophosphamide, Zometa, and Bevacizumab without causing severe side effects in children with recurrent or refractory neuroblastoma.
To find out the side effects seen with the combination of IV and oral cyclophosphamide, Zometa, and Bevacizumab.
To determine if your tumor gets smaller after treatment with the combination of IV and oral cyclophosphamide, Zometa, and Bevacizumab.
To learn about the effects on the development of blood vessels in children receiving this combination of intravenous and oral cyclophosphamide, Zometa, and Bevacizumab.
To learn about the effects on the bones of children receiving this combination of intravenous and oral cyclophosphamide, Zometa, and Bevacizumab.
To measure the effects of this immune system of this combination of combination of intravenous and oral cyclophosphamide, Zometa, and Bevacizumab.

Study Procedures

Cyclophosphamide will be taken two ways. It will be given through an IV once at the beginning of each course. Then it will be taken by mouth once a day, every day for the rest of the course. The medicine by mouth will either be a liquid or a pill.

Zometa is given through an IV over 15 minutes every 4 weeks.

Bevacizumab is given through an IV every 2 weeks. Bevacizumab is not given in the first course of treatment and will be started on the second course. The first time the dose is given it will take approximately 90 minutes to give. The next time the dose is given, the time will be shorter.

All patients should take calcium and Vitamin D to reduce the chances of some side effects caused by the Zometa.

Criteria that need to be met to participate in this study

Patients must be no more 30 years of age when enrolled on study.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
Patients must have adequate heart, kidney, liver blood clotting and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
Patients must have recovered from all prior chemotherapy and surgical procedures

Patients cannot participate in the study if:

They are known to be sensitive to Bevacizumab.
They have a history of very high blood pressure which required intensive intervention
They are pregnant or breastfeeding
Neuroblastoma is present in the brain on a CT or MRI scan done at study entry. Patients with neuroblastoma found in the bones of the skull are eligible if there is no tumor mass associated with them pressing on the brain.
They have a history non healing wounds

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