TARGETED I-131 MIGB THERAPY FOR NEUROBLASTOMA Neuroblastoma is a cancer of the peripheral nervous system and the most common tumor in children. Approximately 600 patients are diagnosed per year. One of the most difficult parts of treating neuroblastoma is that it often initially responds to chemotherapy, radiation and surgery but eventually comes back. The survival at five years from diagnosis is less than 40%. For patients who experience a relapse of their neuroblastoma, the survival is generally accepted to be less than 20%.

The commitment to clinical research in the Cook Children’s Hematology and Oncology Center stems from the desire to provide hope for our patients and a chance for a cure. For many patients, this hope is delivered in the form of clinical trials where patients have access to the most cutting edge treatments. One such treatment is 131I-metaiodobenzylguanidine (MIBG) which is a radioactive target of neuroblastoma. This drug is infused intravenously and goes to the tumor sites, even those that cannot normally be detected, and delivers a radiation dose over an extended period of time directly to tumor cells. The remainder of the radioactive material is then eliminated from the body. The therapy requires specialized facilities for delivery and monitoring of the patient and caregivers to assure that the radiation is being eliminated at the proper rate. The monitoring of the radiation exposure to the whole body is called dosimetry and is performed by nuclear medicine physicists. They measure the radiation emissions from the patient over time as collected by a Geiger counter mounted above the patient bed. Patients are in isolation during for 3-5 days after the infusion until their radiation levels reach a certain threshold. Their visitation from family members is restricted to appropriate exposure levels and then is increased over time as the radiation emissions decrease. MIBG has been shown to be an effective agent in relapsed and refractory neuroblastoma with response rates up to 40% in a heavily pretreated population.

Presently, the MIGB therapy is offered at only five institutions in the United States (University of San Francisco, University of Michigan, Cincinnati Children’s, Dana Farber Cancer Institute, and Children’s Hospital of Philadelphia) and patients must travel to one of these sites for this specialized therapy. Many Cook Children’s patients have traveled to receive this treatment and we are even able to boast several survivors up to the seven year mark. As every year many patients throughout the North and West Texas area travel away from Texas for this therapy, it is our desire to bring this innovative therapy to Cook Children’s Medical Center as the only center of its kind in the entire South and Southwest region.

The MIBG room at Cook Children’s is being constructed on the top floor of the new patient tower and will be the first in Texas to offer MIBG therapy to children with relapsed neuroblastoma. It will feature lead bricks lining the room to contain the radiation within. It will also have an adjacent parent room where the parent can be as accessible as possible to the child while maintaining appropriate radiation safety guidelines. The design of this room has been considered with many factors in mind, particularly maintaining parent/child contact while adhering to radiation safety guidelines. The parents will be integral to the care of the child during this treatment as staff exposure to patients is limited.

The neuroblastoma program has already received national recognition and is a member of a dedicated clinical trials organization for discovery of new therapeutic agents for neuroblastoma (New Approaches to Neuroblastoma Therapy = NANT). NANT is currently comprised of 15 member institutions. This participation has given us the opportunity to participate in clinical trials through this organization that utilize MIBG therapy and has been a catalyst for us to be select invitees to participate in industry sponsored clinical trials. Our participation is presently limited to the pre- and post- MIBG portion of the trial and patients must select another MIBG treatment center for that portion of the therapy. Once the MIBG facility and program are activated we have an immediate venue to participate in these trials. The current three trials utilizing MIBG are outlined below. We are in need of assistance in the expertise of radiation oncologists and radiation physicists to assist with this critical piece of the program.

The success of MIBG in patients with the poorest outcomes have driven investigators in the Children’s Oncology Group and NANT to plan for the incorporation of this treatment into frontline therapy for neuroblastoma in as soon as two years. With the construction of our MIBG treatment center, Cook Children’s will be prepared to accept referrals from across the country as patients approach the MIBG portion of their therapy.

To accomplish the aim of bringing new innovative technology and clinical trials to Cook Children’s, several components must first be in place. We must first assemble the expertise across the Cook Children’s system for a formalized multidisciplinary “MIBG Team.” We must then undertake the necessary intellectual steps to develop our own institutional processes and procedures and validate the dosimetry models.

The Hyundai Hope on Wheels Scholars Program will help support the creation of the program and multidisciplinary team to deliver MIBG therapy at Cook Children’s Medical Center in addition to bringing clinical trials associated with this treatment. The goals of the project are as follows:

Part 1

Implement an I-131 MIBG treatment center at Cook Children’s Medical Center for patients with relapsed or refractory neuroblastoma

1. Form a multidisciplinary clinical MIBG team across the Cook Children’s System that includes Hematology/Oncology physicians, nurses, nuclear medicine, radiation safety and Radiation Oncologists;

2. Develop standardized MIBG SOPs and treatment and training guidelines among team members including physicians, nurses, nuclear medicine, radiation safety and radiation oncology;

3. Validate the whole body radiation dosimetry following MIBG infusion.



Part 2

To implement the MIBG treatment portion of national cooperative group clinical trials and multi-institutional trials at Cook Children’s Medical Center in which we are already currently participating as non-MIBG sites

1. NANT protocol: Irinotecan and Vincristine with 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma;

2. NANT protocol: Vorinostat With 131I-MIBG Therapy For Resistant/Relapsed Neuroblastoma: A Phase I Study;

3. Industry Sponsored Trial: A Phase 2b Study Evaluating the Efficacy and Safety of Ultratrace™ Iobenguane I 131 Among Patients With Relapsed/Refractory High-Risk Neuroblastoma.