Phase I Study of Intratumoral Photodynamic Therapy in Children with NF1 and Plexiform Neurofibromas

Principal Investigator: FISHER, MICHAEL
Program: NFRP
Proposal Number: NF073119
Award Number: W81XWH-08-1-0051
Funding Mechanism: New Investigator Award
Partnering Awards:
Award Amount: $423,545.94


Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders. Plexiform neurofibromas (PN) grow along peripheral nerves and occur with great frequency in NF1. These tumors often cause pain, disfigurement, and functional impairment and can be life-threatening. Complete tumor removal with surgery is the only known effective treatment, but this is rarely possible. Newer medications proposed for future studies may slow or stop growth but are not likely to shrink large PN. Photodynamic therapy (PDT), or light therapy, uses a drug called a photosensitizer and a particular type of light. When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells. In this study, we are testing the photosensitizer LS11 along with an implantable light source that will be placed inside the tumor through a small cut made on the skin surface. The goal is to limit the "treatment effect" to just the tumor. This approach should minimize side effects elsewhere in the body. Neither LS11 nor the implantable light source is approved for marketing by the U.S. Food and Drug Administration. However, studies in adults with different types of cancer have shown this approach to be well tolerated and to result in a decrease in tumor size in many patients.

The focus of this study is to evaluate the safety of this treatment for children and young adults with PN. If PDT with one implantable light source is shown to be safe, we will evaluate the safety and feasibility of using multiple light sources to treat larger PN. We expect that this treatment will be effective for patients with PN. We will assess whether this treatment shrinks the tumor and improves the quality of life for patients with PN; however, definitive evaluation of the effectiveness of this therapy can only be done once safety is shown. A follow-up study of the effectiveness of this therapy is planned.

In addition, patients enrolled later in the study will be offered the opportunity to have their PN tumor biopsied at the same time the intratumoral light source is placed. This can be done without substantial increased risk to the patient. Under normal circumstances, the ability to obtain PN biopsy tissue for research study is low. Therefore, we know little about the biology of these tumors. In this study, tissue will be frozen and stored for use in future studies to identify molecular abnormalities that may be potential targets for future therapies.