Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors
Status: | Completed |
---|---|
Conditions: | Brain Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | Any - 18 |
Updated: | 2/27/2019 |
Start Date: | March 2013 |
End Date: | June 29, 2018 |
Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study
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.
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.
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.
We found this trial at
1
site
Wauwatosa, Wisconsin 53226
Principal Investigator: Harry T Whelan, MD
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