Clinical trial NCT01682746: Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors
Official title: Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Tumor, Recurrent
Keywords: Brain Tumor
Photodynamic Therapy
Photochemotherapy
Astrocytoma
Pilocytic Astrocytoma
Low grade Astrocytoma
Anaplastic Astrocytoma
Glioblastoma
GBM
Chordoma
Germinoma
Germ Cell Tumor
Non-germinaoma
CNS Lymphoma
Craniopharyngioma
Brain Stem Glioma
Ependymoma
Mixed Glioma
Optic Nerve Glioma
Subependymoma
Medulloblastoma
Meningioma
Metastatic Brain Tumors
Oligodendroglioma
Pituitary Tumors
Primitive Neuroectodermal
PNET
Desmoplastic Neuroepithelial Tumor
DNET
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: Pinnacle Biologics Inc.
First posted: 2012-09-11
Enrollment: 5
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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.


Eligibility criteria: 1. Age: ≥ 6 months and \< 18 years
2. Disease: Patients with relapsed or refractory brain tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse. Tumors can be either supratentorial or infratentorial (posterior fossa) in location.
3. Disease Status: Patients must have potentially resectable disease.
4. Therapeutic Options: Patients' current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
5. Performance Level: Karnofsky 50% or greater for patients \> 16 years of age and Lansky 50 or greater for patients \< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
6. Predictable Life Expectancy: \> 8 weeks
7. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy. At least 3 weeks from previous chemotherapy and 4 weeks from prior radiation therapy
8. Organ Function:

   Adequate bone marrow function

   Absolute neutrophil count ≥ 1,000

   Platelet count ≥ 100,000 (may transfuse to meet requirement)

   Adequate renal function

   Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 OR

   A serum creatinine within normal range based on age/gender

   Adequate liver function Bilirubin (direct) ≤ 3X upper limit of normal (ULN) for age

   SGPT (ALT) ≤ 10X ULN

   For the purpose of this study, the ULN for SGPT is 45 U/L

   Serum albumin ≥ 2 g/dL

   Adequate coagulation

   PT and INR ≤ 2X ULN for age
9. Central Nervous System Function: Patients with seizure disorder may be enrolled if receiving non- enzyme inducing anticonvulsants and well controlled.
10. Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
11. Archival tumor tissue slides from initial diagnosis should be reviewed by CHW institutional pathologists prior to study enrollment whenever possible.

Exclusion Criteria

1. Disseminated disease (metastatic disease)
2. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study, as risks of fetal and teratogenic adverse effects of Photofrin® are not known.
3. Other concurrent tumor therapy
4. Subjects with porphyria
5. Subjects taking potentially photosensitizing drugs
6. The presence of adverse events of neurologic function, photosensitivity, or photophobia Grade 4 or higher (CTCAE Version 4.0)
7. Allergy to eggs, soybean oil, or safflower oil (due to potential allergy against intralipids)
8. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.

Primary outcomes:
measure: Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects
timeFrame: One to four weeks from PDT
Secondary outcomes:
measure: Brain tumor response
timeFrame: Response ocurring within 3 years after PDT
Other outcomes:
Locations:
city: Wauwatosa
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Harry T Whelan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Jeff Knipstein, MD
role: PRINCIPAL_INVESTIGATOR
References: