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Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01966809
Recruitment Status : Terminated (Insufficient enrollment.)
First Posted : October 22, 2013
Results First Posted : August 8, 2019
Last Update Posted : August 20, 2019
Pinnacle Biologics Inc.
Information provided by (Responsible Party):
Harry T Whelan, MD, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE October 17, 2013
First Posted Date  ICMJE October 22, 2013
Results First Submitted Date  ICMJE July 18, 2019
Results First Posted Date  ICMJE August 8, 2019
Last Update Posted Date August 20, 2019
Study Start Date  ICMJE June 2015
Actual Primary Completion Date December 19, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2015)
Six Month Relapse-free Survival (RFS). [ Time Frame: Six months from PDT ]
Relapse free survival is the proportion of subjects who have gone six months since PDT without the disease getting worse.
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2013)
Maximum tolerable dose (MTD) of Photofrin® [ 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: 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. Photosensitivity: defined as a photosensitivity adverse event (CTCAE category dermatology/skin) of grade 4 occurring within the same period. Ocular sensitivity: Photofrin®-induced ocular sensitivity is defined as a photophobia adverse event (CTCAE category ocular/visual) of grade 4 within the same period. Any other toxicity of CTCAE grade 4 or higher within the same period.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2015)
  • Remission Rate. [ Time Frame: Three years from PDT ]
    To obtain preliminary data toward determining whether this combination results in higher remission rate when compared to historical data.
  • Progression-free Survival and Overall Survival. [ Time Frame: Three years from PDT ]
    To further explore and report progression-free survival and overall survival for three years post PDT treatment.
  • Tumor Response. [ Time Frame: Six months from PDT ]
    To measure complete response, partial response, stable disease or progressive disease using the response assessment for Neuro-Oncology (RANO) criteria with the follow-up medical imaging, which specifically incorporates volumetric measurements of brain tumor enhancement and clinical measures of neurological decline and to compare these outcomes to historical controls.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2013)
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. 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. 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. Stable Disease (SD): Not CR, PR, or Progressive Disease (PD). Progressive Disease (PD): Progressive disease is defined as >25% increase in any involved site; or appearance of new lesions.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 17, 2013)
  • 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).
  • 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 High Grade Gliomas
Official Title  ICMJE A Phase II Study of Photodynamic Therapy (PDT) With Photofrin® (IND 104,613) For Recurrent High Grade Gliomas in Adults
Brief Summary

This study will be aimed at investigating the effectiveness of a treatment for brain tumors called Photodynamic Therapy, or PDT. Briefly, a subject will receive a light-sensitive drug, called Photofrin®, the day before a tumor removal surgery. The next day, after the tumor is removed, red light from a laser will be shone into the tumor cavity through a light-diffusing sphere. This light will activate the photosensitizer, and possibly kill any tumor cells that may be left.

We plan to measure how long the subject may go without a new tumor regrowth, and overall how long subjects survive. We will compare these results to typical results to see if we are seeing any improvements.

Objective: To define the antitumor activity of Photofrin® and laser light activation within the confines of a Phase II study.

Detailed Description

Photodynamic therapy (PDT) is a well-known treatment for other type of tumors; however it is an experimental treatment for brain tumors. There is much we do not know about the effectiveness of PDT in patients with brain tumors. The purpose of this study is to define the antitumor activity of Photofrin® and laser light activation. Photofrin® is a photosensitizing drug (a dye that is activated by light) used in PDT. We want to test the activity of PDT and to see what are the effects (good and bad) on you and your brain tumor. We also want to learn if this treatment will cause brain tumors to shrink and whether it will help patients with brain tumors to live longer.

PDT is a cancer treatment that involves giving a photosensitive dye (Photofrin®), into your vein through a tube (called an IV). This dye will go inside of the cancer cells more than it will go inside the normal, healthy cells. PDT using Photofrin® is an approved treatment in patients with certain types of cancer such as lung, and esophageal (from the mouth to the stomach) cancers.

Everyone in this study will receive Photofrin® (porfimer sodium) for injection (Pinnacle Biologics, Inc., Bannockburn, IL, USA), and be treated with red light emitted by a red laser. The light will be sent from the laser to the surface of the brain where the tumor is located using a light transmitting fiber. The fiber will have a knob at the end that spreads the light out evenly in all directions.

Previous studies have shown that patients with malignant brain tumors called gliomas had a good response to PDT. The patients in these studies lived longer than they were expected to live. In one study of adults with brain tumors in Australia, patients given PDT had greatly improved survival rates. Fifty seven percent (57%) of the patients with gliomas called anaplastic astrocytoma survived for 36 months. Thirty seven percent (37%) of the patients with gliomas called glioblastoma multiforme survived for 36 months. Froedtert Hospital, in Milwaukee WI, has been involved in PDT studies in adults in the past. This current study is is being done in a very similar way to the study done in Australia, and will use increased Photofrin®) and light doses than our previous study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain Tumor, Recurrent
Intervention  ICMJE Drug: Photofrin photodynamic therapy.

The subjects will receive a dose of 2.5 mg/kg of Photofrin intravenously 24 hours before planned surgical resection. Tumor resection will be carried out in the standard fashion in order to achieve the maximum tumor resection compatible with preservation of neurological function. After resection, Intralipid will be infused into the craniotomy and kept for approximately 45 min, while PDT will be performed. The illumination time will be calculated from the power density (mW) emitted by the laser and the radius (r) of the cavity to deliver a total light dose of 240 J/cm2 at a using the following formula:

Treatment Time (sec) = Light dose (J/cm2) x Cavity surface (cm2) x 1000 Power density (mW) Cavity Surface (cm2) = 4 x 3.14 x r2 The optical fiber will be placed in the center of the surgical cavity and photoillumination will commence. After PDT, the Intralipid solution will be removed and the wound will be closed. The subject will be sent to the intensive care area for recovery.

Study Arms  ICMJE Experimental: Photofrin photodynamic therapy.
Photofrin photodynamic therapy. Drug - 2.5 mg/kg, light - 240 mJ/cm2.
Intervention: Drug: Photofrin photodynamic therapy.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 18, 2019)
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2013)
Actual Study Completion Date  ICMJE December 19, 2017
Actual Primary Completion Date December 19, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Age: Greater than or equal to 18 years of age.
  2. Disease: Patients with relapsed or refractory high grade glioma are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse. Tumors must be supratentorial in location.
  3. Disease Status: Patients must have potentially resectable disease.
  4. Therapeutic Options: Patient's 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. 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: > 8weeks
  7. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy. At least three weeks from previous chemotherapy and 4 weeks from prior radiation therapy.
  8. Organ Function:

    a. Adequate bone marrow function i. Absolute neutrophil count ≥ 1,000 ii. Platelet count ≥ 100,000 (may transfuse to meet requirement) b. Adequate renal function i. Creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73 m2 or ii. A serum creatinine within normal range based on age/gender. c. Adequate liver function i. Bilirubin (direct) ≤ 3X upper limit of normal (ULN) for age ii. SGPT (ALT) ≤ 10X ULN. For the purpose of this study, the ULN for SGPT is 45 U/L.

    iii. Serum albumin ≥ 2 g/dL. d. Adequate coagulation i. 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 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 Froedtert Health-MCW neuropathologist prior to study enrollment whenever possible.

Exclusion Criteria

  1. Disseminated 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 (Appendix 3)
  6. The presence of adverse events of neurologic function, photosensitivity, or photophobia Grade 4 or higher (CTCAE Version 4.02).47
  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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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 NCT01966809
Other Study ID Numbers  ICMJE PRO00023580
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE 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
PRS Account Medical College of Wisconsin
Verification Date August 2019

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