Photodynamic Therapy (PDT) for 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.
|Study Design:||Endpoint Classification: Safety Study
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 ] [ Designated as safety issue: Yes ]
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 5 years after PDT and persisting for 4 weeks. ] [ Designated as safety issue: No ]
The brain tumor imaging response will be assessed on the change in tumor maximum diameter.
Continuous Complete Response (CCR): Diameter remains= 0 after gross total resection (GTR) of the tumor.
- Complete Response (CR): Diameter = 0. A complete response will be said to occur when there is disappearance of all clinical evidence of disease and of all disease noted by non-invasive testing and re-staging for a minimum of four weeks.
- Partial Response (PR): Axial or coronal diameter reduction of >25% of first post-PDT contrast enhanced CT or MRI. A partial response is defined as lasting for a minimum of four weeks. No simultaneous increase in the size of any other lesion or appearance of any new lesion may occur.
- Stable Disease (SD): Not CR, PR, or Progressive Disease (PD).
- Progressive Disease (PD): Progressive disease is defined as >25% increase in any involved site; or appearance of new lesions.
- Brain tumor time to progression [ Time Frame: Five years from PDT ] [ Designated as safety issue: No ]
Progression Free Survival Progression-free survival (PFS) will based only on whether the patient has evidence of disease progression or recurrence. Current standard to document disease progression or recurrence is radiographic evaluation. Magnetic resonance imaging (MRI) is the current optimal method to detect gross tumor changes. We will assess for disease progression or tumor recurrence using MRI.
Criteria for disease progression or recurrence:
Increase on MRI of at least 25% in the product of perpendicular diameters of any residual tumor lesion left after PDT intervention.
Or, Evidence of any new lesions.
Or, Evidence of tumor cells in evaluation of Cerebrospinal fluid (CSF).
- Survival Time [ Time Frame: Five years from PDT ] [ Designated as safety issue: No ]Survival times are defined as follows: Days (weeks) after brain tumor PDT, and days (weeks) after first surgical treatment (diagnosis).
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||April 2021|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Photofrin (porfimer sodium) photodynamic therapy.
Drug: Photofrin (porfimer sodium) photodynamic therapy.
Subjects will receive a selected dose of either 0.5, 1.3, 2.0, or 3.0 mg kg−1 of Photofrin IV 24hr prior to PDT. Craniotomy and tumor resection (removal) will be carried out in the standard fashion. After tumor resection, Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniformity of delivery. Photoactivation of PHOTOFRIN is controlled by the total light dose delivered over the treatment time. The illumination time will be calculated to deliver a total light dose (energy) of 240 J/cm2 at a wavelength of 630nm. The subject's head will be positioned on the operating table such that the tumor cavity is uppermost. The optical fiber will be placed in the approximate center of the surgical cavity and photoillumination will commence. After PDT, the wound will be closed. The subject will be extubated, recovered from anesthesia, and then sent to the intensive care area for appropriate observation.
|Contact: Michael Kelly, MDfirstname.lastname@example.org|
|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:||Michael Kelly, MD||Medical College of Wisconsin|