Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors
The goal of this proposal is to evaluate a new Photodynamic Therapy (PDT) modification which could revolutionize the treatment of brain tumors in children and adults. There are currently few cases published involving the use of PDT in infratentorial (in the posterior fossa) brain tumors in general and specifically those occurring in children. The investigators propose to test a technique, for the first time in the U.S., that demonstrated in Australian adult glioblastoma patients dramatic long-term, survival rates of 57% (anaplastic astrocytoma) and 37% (glioblastoma multiforme). These results are unprecedented in any other treatment protocol.
Photodynamic therapy (PDT) is a paradigm shift in the treatment of tumors from the traditional resection and systemic chemotherapy methods. The principle behind photodynamic therapy is light-mediated activation of a photosensitizer that is selectively accumulated in the target tissue, causing tumor cell destruction through singlet oxygen production. Therefore, the photosensitizer is considered to be the first critical element in PDT procedures, and the activation procedure is the second step. The methodology used in this proposal utilizes more intensive laser light and larger Photofrin photosensitizer doses than prior PDT protocols in the U.S. for brain tumor patients. The PDT will consist of photoillumination at 630 nm beginning at the center of the tumor resection cavity, and delivering a total energy of 240 J cm−2. The investigators feel that the light should penetrate far enough into the tissue to reach migrating tumor cells, and destroy these cells without harming the healthy cells in which they are dispersed.
The investigators will be testing the hypothesis that pediatric subjects with progressive/recurrent malignant brain tumors undergoing PDT with increased doses of Photofrin® and light energy than were used in our previous clinical study will show better progression free survival (PFS) and overall survival (OS) outcomes. PDT will also be effective against infratentorial tumors. The specific aims include determining the maximum tolerable dose (MTD) of Photofrin in children and looking for preliminary effectiveness trends.
|Brain Tumor, Recurrent||Drug: Photofrin (porfimer sodium) & photodynamic therapy.||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study|
- Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects [ Time Frame: One to four weeks from PDT ]
MTD is defined as the Photofrin® dose that precedes the dose level used with a subgroup of subjects that exhibits a greater than 33% DLT occurrence.
DLT is defined as any of the following events with reasonable possibility to be attributable to the experimental intervention:
- Neurotoxicity: defined as a decline in neurological function manifest within 1 week of PDT and persistent to 4 weeks post-PDT. Adverse events of neurologic function of grade 4, or a level change from grade 1 to grade 3, within this period will constitute neurotoxicity for this study. The CTCAE V4.02 will be used.
- Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period.
- Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period.
- Any other toxicity of CTCAE grade 4 or higher within the same period.
- Brain tumor response [ Time Frame: Response ocurring within 3 years after PDT ]To preliminarily define the antitumor activity of Photofrin and laser light activation within the confines of a Phase 1 Study. We will follow progression free survival and overall survival for 3 years post PDT treatment.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||April 2024|
|Estimated Primary Completion Date:||April 2019 (Final data collection date for primary outcome measure)|
Photofrin (porfimer sodium) photodynamic therapy.
Drug: Photofrin (porfimer sodium) & photodynamic therapy.
Intravenous (IV) Photofrin
This is a dose escalation study. Patients will receive Photofrin via an IV infusion approximately 24 hours prior to their tumor resection surgery and Photodynamic Therapy (PDT). Patients will be light sensitive immediately upon receiving the Photofrin and must observe photosensitivity & light precautions for a minimum of 30 days after the infusion.
Photodynamic Therapy (PDT)
After tumor resection, an optical fiber will be placed in the approximate center of the surgical cavity. Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniform delivery. Photoactivation of Photofrin is controlled by the total light dose delivered over the treatment time.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682746
|Contact: Jeff Knipstein, MDfirstname.lastname@example.org|
|Contact: Shelly Leveque, RNemail@example.com|
|United States, Wisconsin|
|Children's Hospital of Wisconsin||Recruiting|
|Wauwatosa, Wisconsin, United States, 53226|
|Principal Investigator: Harry T Whelan, MD|
|Principal Investigator:||Harry T Whelan, MD||Medical College of Wisconsin|
|Principal Investigator:||Jeff Knipstein, MD||Medical College of Wisconsin|