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Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors

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ClinicalTrials.gov Identifier: NCT01682746
Recruitment Status : Completed
First Posted : September 11, 2012
Last Update Posted : February 25, 2019
Sponsor:
Collaborator:
Pinnacle Biologics Inc.
Information provided by (Responsible Party):
Harry T Whelan, MD, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE September 5, 2012
First Posted Date  ICMJE September 11, 2012
Last Update Posted Date February 25, 2019
Study Start Date  ICMJE March 2013
Actual Primary Completion Date June 29, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01682746 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2014)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
  • Brain tumor response [ Time Frame: Response ocurring within 5 years after PDT and persisting for 4 weeks. ]
    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 ]
    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).
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE
 (submitted: September 10, 2012)
Survival Time [ Time Frame: Five years from PDT ]
Survival times are defined as follows: Days (weeks) after brain tumor PDT, and days (weeks) after first surgical treatment (diagnosis).
 
Descriptive Information
Brief Title  ICMJE Photodynamic Therapy (PDT) for Recurrent Pediatric Brain Tumors
Official Title  ICMJE Photodynamic Therapy (PDT) for Poor Prognosis Recurrent/Refractory Malignant Brain Tumors - A Phase I Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Tumor, Recurrent
Intervention  ICMJE 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.

Study Arms Experimental: Treatment
Photofrin (porfimer sodium) photodynamic therapy.
Intervention: Drug: Photofrin (porfimer sodium) & photodynamic therapy.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 21, 2019)
5
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2012)
24
Actual Study Completion Date June 29, 2018
Actual Primary Completion Date June 29, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  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.
Sex/Gender
Sexes Eligible for Study: All
Ages 6 Months to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01682746
Other Study ID Numbers  ICMJE 163588-1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Harry T Whelan, MD, Medical College of Wisconsin
Study Sponsor  ICMJE Harry T Whelan, MD
Collaborators  ICMJE Pinnacle Biologics Inc.
Investigators  ICMJE
Principal Investigator: Harry T Whelan, MD Medical College of Wisconsin
Principal Investigator: Jeff Knipstein, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP