Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors

NCT01682746 | Completed Phase 1 DMC

• 1 other identifier: 163588-1
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects

  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 Outcomes (1)

• Brain tumor response

  Response ocurring within 3 years after PDT

Study Arms (1)

Treatment

EXPERIMENTAL

Photofrin (porfimer sodium) photodynamic therapy.

Drug: Photofrin (porfimer sodium) & photodynamic therapy.

Interventions

Photofrin (porfimer sodium) & photodynamic therapy. DRUG

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.

Treatment

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may not qualify if:

• Disseminated disease (metastatic disease)
• 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.
• Other concurrent tumor therapy
• Subjects with porphyria
• Subjects taking potentially photosensitizing drugs
• The presence of adverse events of neurologic function, photosensitivity, or photophobia Grade 4 or higher (CTCAE Version 4.0)
• Allergy to eggs, soybean oil, or safflower oil (due to potential allergy against intralipids)
• 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.

Sponsors & Collaborators

• Harry T Whelan, MD: lead
• Pinnacle Biologics Inc.: collaborator

Study Sites (1)

Children's Hospital of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Astrocytoma; Glioblastoma; Chordoma; Germinoma; Neoplasms, Germ Cell and Embryonal; Craniopharyngioma; Ependymoma; Glioma; Optic Nerve Glioma; Glioma, Subependymal; Medulloblastoma; Meningioma; Oligodendroglioma; Pituitary Neoplasms; Neuroectodermal Tumors, Primitive

Interventions

Dihematoporphyrin Ether; Photochemotherapy

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Optic Nerve Neoplasms; Cranial Nerve Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Diseases; Optic Nerve Diseases; Eye Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Endocrine Gland Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hematoporphyrin Derivative; Hematoporphyrins; Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pigments, Biological; Biological Factors; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Study Officials

• Harry T Whelan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Jeff Knipstein, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Bleser Professor of Neurology

Study Record Dates

• First Submitted: September 5, 2012
• First Posted: September 11, 2012
• Study Start: March 1, 2013
• Primary Completion: June 29, 2018
• Study Completion: June 29, 2018
• Last Updated: February 25, 2019

Record last verified: 2019-02

Locations

US (1)