Clinical Trial: Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study

Brief Summary:

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 Phot

Detailed Summary:
Sponsor: Harry T Whelan, MD

Current Primary Outcome: 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:

  1. 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.
  2. Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period.
  3. Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period.
  4. Any other toxicity of CTCAE grade 4 or higher within the same period.


Original Primary Outcome: Same as current

Current Secondary Outcome: 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.


Original Secondary Outcome:

  • Brain tumor response [ Time Frame: Response ocurring within 5 years after PDT and persisting for 4 weeks. ]

    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.

    1. 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.
    2. 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.
    3. Stable Disease (SD): Not CR, PR, or Progressive Disease (PD).
    4. 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 ]

    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).



Information By: Medical College of Wisconsin

Dates:
Date Received: September 5, 2012
Date Started: March 2013
Date Completion: April 2024
Last Updated: January 16, 2017
Last Verified: January 2017