Clinical Trial: Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using LS11 in Children With Plexiform Neurofibromas
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using Intratumoral Delivery of Non-coherent Light for Photoactivation of LS11 in Children With Plexiform Neurof
Brief Summary:
Plexiform neurofibromas (PN) represent one of the most significant complications of NF1. They are a significant cause of morbidity in neurofibromatosis type 1 (NF1) by causing pain, impaired function, and disfigurement. They may become life-threatening through mechanical compression of vital organs such as the trachea, great vessels, or spinal cord, and may significantly interfere with normal function when located in the extremities or orbit. The only effective therapy for PN is total surgical excision. However, due to local infiltration of normal tissue, gross total resection is usually not feasible, and often PN are completely unresectable due to their location, size, and multiplicity. To date, other therapeutic modalities, including radiotherapy and chemotherapy, have not shown efficacy in PN.
In the present study, local photodynamic therapy will be investigated. Photodynamic therapy (PDT) utilizes a drug, called a photosensitizer or photosensitizing agent, 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. PDT is expected to result in treatment response with shrinkage of tumor. The main purpose of the study is to determine the maximum amount of light that can be safely used with LS11 for PDT in children with plexiform neurofibromas.
Detailed Summary:
Current treatment options for PN are limited. The only effective therapy for PN is complete surgical resection. Incompletely resected lesions have a high incidence of recurrence, often resulting in the necessity of several surgeries over a patient's lifetime. Development of non-surgical treatments for PN is a high priority. To date, other therapeutic modalities, including radiotherapy and chemotherapy, have not shown efficacy in PN, although it is arguable that these modalities have not been sufficiently studied. Newer approaches, including anti-angiogenesis agents, farnesyl transferase inhibitors, and inhibitors of growth factor pathways are in development and are being studied, but are clearly not proven therapies.
Investigational Agent LS11, talaporfin sodium, was specifically developed as a photosensitizing agent for use in photodynamic therapy. The light activation of LS11 leads to the formation of singlet oxygen causing damage to the vascular endothelial cells leading to vascular thrombosis and occlusion.
Phase I and II studies were conducted in the US and Japan using LS11. PDT with LS11 was generally well tolerated in these studies and there were no serious adverse events noted.
PDT is a novel treatment modality in which a systemically administered photosensitizer (LS11 in our proposal) is activated locally by illuminating the diseased tissue with light of a specific wavelength. Light activation of LS11 leads to the formation of reactive oxygen species that cause damage to the vascular endothelial cells leading to vascular thrombosis and occlusion and subsequently death of tumor cells.
Light Source Placement: Ultrasound may be used to monitor the percutaneous implantation of the Light Source. However, the position of
Sponsor: Children's Hospital of Philadelphia
Current Primary Outcome: To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children. [ Time Frame: Week 4 and 12 ]
Original Primary Outcome: Same as current
Current Secondary Outcome: To evaluate the change in quality of life of treated patients. [ Time Frame: Week 4 and 12 ]
Original Secondary Outcome: Same as current
Information By: Children's Hospital of Philadelphia
Dates:
Date Received: July 14, 2008
Date Started: July 2008
Date Completion:
Last Updated: April 14, 2015
Last Verified: April 2015
