Photodynamic Therapy (PDT) for Brain Tumors

This study is currently recruiting participants.
Verified August 2013 by Medical College of Wisconsin
Sponsor:
Collaborator:
Pinnacle Biologics Inc.
Information provided by (Responsible Party):
Harry T Whelan, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01682746
First received: September 5, 2012
Last updated: August 28, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Brain Tumor, Recurrent
Drug: Photofrin (porfimer sodium) photodynamic therapy.
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Maximum tolerable dose (MTD) of Photofrin® in pediatric subjects [ Time Frame: One to four weeks from PDT ] [ Designated as safety issue: Yes ]

    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.


Secondary Outcome Measures:
  • 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).



Other Outcome Measures:
  • Survival Time [ Time Frame: Five years from PDT ] [ Designated as safety issue: No ]
    Survival times are defined as follows: Days (weeks) after brain tumor PDT, and days (weeks) after first surgical treatment (diagnosis).


Estimated Enrollment: 24
Study Start Date: March 2013
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Photofrin (porfimer sodium) photodynamic therapy.
Drug: Photofrin (porfimer sodium) photodynamic therapy.
Subjects will receive a selected dose of either 0.5, 1.3, 2.0, or 3.0 mg kg−1 of Photofrin IV 24hr prior to PDT. Craniotomy and tumor resection (removal) will be carried out in the standard fashion. After tumor resection, Intralipid will be infused into the open tumor cavity while PDT is performed. The Intralipid will diffuse the light and ensure uniformity of delivery. Photoactivation of PHOTOFRIN is controlled by the total light dose delivered over the treatment time. The illumination time will be calculated to deliver a total light dose (energy) of 240 J/cm2 at a wavelength of 630nm. The subject's head will be positioned on the operating table such that the tumor cavity is uppermost. The optical fiber will be placed in the approximate center of the surgical cavity and photoillumination will commence. After PDT, the wound will be closed. The subject will be extubated, recovered from anesthesia, and then sent to the intensive care area for appropriate observation.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01682746

Contacts
Contact: Michael Kelly, MD 414-266-2091 mekelly@mcw.edu

Locations
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Wauwatosa, Wisconsin, United States, 53226
Principal Investigator: Harry T Whelan, MD         
Sponsors and Collaborators
Harry T Whelan, MD
Pinnacle Biologics Inc.
Investigators
Principal Investigator: Harry T Whelan, MD Medical College of Wisconsin
Principal Investigator: Michael Kelly, MD Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: Harry T Whelan, MD, Bleser Professor of Neurology, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01682746     History of Changes
Other Study ID Numbers: 163588-1
Study First Received: September 5, 2012
Last Updated: August 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:
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

Additional relevant MeSH terms:
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Trioxsalen
Dihematoporphyrin Ether
Hematoporphyrin Derivative
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 15, 2014