Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors

February 21, 2019 updated by: Harry T Whelan, MD

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Children's Hospital of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

9 months to 16 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Photofrin (porfimer sodium) photodynamic therapy.
Drug: Photofrin (porfimer sodium) & photodynamic therapy.

Intravenous (IV) Photofrin

This is a dose escalation study. Patients will receive Photofrin via an IV infusion approximately 24 hours prior to their tumor resection surgery and Photodynamic Therapy (PDT). Patients will be light sensitive immediately upon receiving the Photofrin and must observe photosensitivity & light precautions for a minimum of 30 days after the infusion.

Photodynamic Therapy (PDT)

After tumor resection, an optical fiber will be placed in the approximate center of the surgical cavity. Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniform delivery. Photoactivation of Photofrin is controlled by the total light dose delivered over the treatment time.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
One to four weeks from PDT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Response ocurring within 3 years after PDT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Harry T Whelan, MD

Collaborators

Pinnacle Biologics Inc.

Investigators

  • Principal Investigator: Harry T Whelan, MD, Medical College of Wisconsin
  • Principal Investigator: Jeff Knipstein, MD, Medical College of Wisconsin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Actual)

June 29, 2018

Study Completion (Actual)

June 29, 2018

Study Registration Dates

First Submitted

September 5, 2012

First Submitted That Met QC Criteria

September 10, 2012

First Posted (Estimate)

September 11, 2012

Study Record Updates

Last Update Posted (Actual)

February 25, 2019

Last Update Submitted That Met QC Criteria

February 21, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 163588-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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