Photodynamic Therapy (PDT) for Brain Tumors

• 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.

  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 ] [ 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).

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.

Inclusion Criteria:

Subjects with malignant brain tumors will be selected for photodynamic therapy if they meet all of the following criteria.

1. Age: 6 months-18 years.
2. Location of tumor: supra- or infratentorial brain (localized, non-disseminated) with negative CSF.
3. Tumor type: primary, or solitary metastasis, recurrent (or progressive), and resectable.

4. MRI/CT scan characteristics:

   • measurable tumor mass
   • single or multiple masses accessible to light administration.
5. Subjects must have been failed by standard therapy including radiation therapy.
6. Informed consent of subject and/or the patient's legally acceptable representative.
7. Predicted life expectancy more than or equal to 8 weeks.
8. May transfuse platelets. ANC (absolute neutrophil count) more than 1,000/cmm. Coags (PT, PTT) normal.

9. Adequate renal function defined as:

   • Creatinine or radioisotope GFR more than or equal to 70 ml/min/1.73m2 or
   • A serum creatinine based on age/gender within normal limits.

10. Adequate liver function defined as:

    • Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 times the upper limit of normal (ULN) for age.
    • SGPT (ALT) less than or equal to 110 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L.
    • Serum albumin more than or equal to 2 g/dL.

Exclusion Criteria:

Subjects will be excluded from participation in the study on the basis of the following:

1. Life expectancy of less than 8 weeks.
2. Pregnancy.
3. Inability to consent.
4. Previous brachytherapy.
5. Previous chemotherapy within 4 weeks of enrollment.
6. Other concurrent tumor therapy.
7. Subjects with porphyria.
8. Subjects taking tetracycline, sulfonamides, phenothiazines, sulfonylureas, thiazides, griseofulvin, fluoroquinolones, or any other potentially photosensitizing drugs.
9. Previous radiation therapy within 8 weeks of enrollment.
10. The presence of adverse events of neurologic function, photosensitivity, or photophobia grade 4 or higher (CTCAE Version 4.02).
11. Karnofsky functional status or Lansky play scale score of less than 50.
12. Allergy to eggs, soybean oil, or safflower oil.