Photodynamic Therapy for the Treatment of Vertebral Metastases
Primary Purpose
Vertebral Metastases
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Visudyne
Sponsored by
About this trial
This is an interventional treatment trial for Vertebral Metastases
Eligibility Criteria
Inclusion Criteria:
- Age between 20 and 85
- Established metastatic vertebral bony disease in the spine
- Eligible for single level vertebral osteoplasty (i.e. percutaneous vertebroplasty, kyphoplasty)
- Patients who are symptomatic with axial pain from vertebral metastatic involvement and are at risk for pathologic fracture; or have had a symptomatic pathologic fracture
- Patients who have shown radiographic progression and/or pain symptoms of a documented vertebral metastasis despite non-surgical therapies
Exclusion Criteria:
- Progressive neurological compromise
- Osteoblastic vertebral metastatic disease
- Posterior vertebral cortical/body wall involvement
- Spinal canal compromise / neurologic compression
- Anticipated life expectancy of less than twelve weeks to live
- Cognitive impairment and/or language barriers to study participation
- Severe hepatic impairment (Child's C) with active hepatitis or hepatic disease.
- Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. CNS metastases must be stable for > 2 weeks prior to screening.)
- Nursing mothers, pregnant, currently breastfeeding or trying to get pregnant.
- Unable to avoid sun exposure for 5 day post-PDT therapy (per verteporfin precautions).
- Hyperphotosensitivity conditions, including porphyria
- Hypersensitivity to verteporfin or any other ingredients of Visudyne
Sites / Locations
- Sunnybrook Health Sciences Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose escalating PDT
Arm Description
Outcomes
Primary Outcome Measures
Intraoperative dosimetry
Intraoperative dosimetry data on light transmission and attenuation in patient specific diseased bone will be contrasted to pre-operative imaging data and the region of effect based on actual light transmission compared to pre-operative planning algorithms. These results will gauge the potential accuracy of our planning algorithms.
Secondary Outcome Measures
Neurologic function
The primary safety parameter will be unexpected worsening in neurological function.
Physical examination will include a detailed neurological examination (including ASIA score) that assesses the strength, sensation and reflexes of the patient in the upper and lower extremities
Full Information
NCT ID
NCT02464761
First Posted
June 1, 2015
Last Updated
February 14, 2018
Sponsor
Sunnybrook Health Sciences Centre
1. Study Identification
Unique Protocol Identification Number
NCT02464761
Brief Title
Photodynamic Therapy for the Treatment of Vertebral Metastases
Official Title
Photodynamic Therapy (PDT) for the Treatment of Vertebral Metastases: A Prospective Phase I Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
September 7, 2017 (Actual)
Study Completion Date
September 7, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An estimated 10 percent of primary breast, prostate, lung, thyroid and renal cell tumors metastasize to the spine. The majority of these tumors are detected before surgical intervention is required and most patients receive radiation therapy for symptomatic relief. Complete pain control, duration of pain control, high recurrence rates and soft tissue complications make radiation a less than ideal treatment. Also, pre-operative radiation therapy is a significant negative predictor for surgical outcomes. To improve the treatment options for patients with advanced cancer with spinal lesions the research team investigated a new minimally invasive therapy known as photodynamic therapy (PDT) that targets metastatic spine lesions with limited side effects. PDT involves the use of a photo-activated chemotherapeutic agent, given intravenously that when stimulated by non-thermal wavelength-specific light allows for selective ablation of tumor tissue. The light is delivered to the spine through small fiber optic cables using a diode laser. By combining canine and porcine studies the investigators have strong evidence to support that PDT is both safe and effective for the treatment of metastatic tumors in the spine. PDT is targeted, repeatable, minimally invasive and has limited local and systemic side effects. Its use would enhance the treatment options for patients with advanced stage cancer. The goal of the present study is to demonstrate that PDT can be safely and effectively given to treat spinal metastases in patients with advanced stage cancer who have multiple lesions or who have failed radiation or surgical intervention. The effectiveness of this treatment will be determined through clinical and radiographic endpoints along with recurrence and survival. The investigators intend to demonstrate that PDT is a minimally invasive method with low morbidity and mortality by which spinal tumors can be ablated and later stabilized through vertebroplasty, optimizing quality of life and providing effective treatment.
Detailed Description
There are over 1.5 million cases of cancer reported each year in North America and a significant number of patients eventually suffer from metastases to the spine which present as an extremely challenging problem for both the clinician and patient. Primary tumors that most commonly affect the spine include breast, prostate, lung, thyroid and renal cell cancer. Estimates from large clinical series report at least a 10 percent rate of metastases to the spine from these most common tumors. These lesions are extremely painful and significantly affect the quality of life of advanced stage cancer patients. The majority of these tumors are detected before surgical intervention is required and most patients receive radiation therapy for their spine lesions for symptomatic relief. However, complete pain control, duration of pain control along with a high recurrence rate of lesions and soft tissue complications makes radiation a less than an ideal treatment. In addition, pre-operative radiation therapy is a significant negative prognosticator for surgical outcomes.
To improve the treatment options for patients with advanced cancer with spinal lesions the research team has investigated a new minimally invasive therapy, known as photodynamic therapy (PDT) that targets metastatic spine lesions directly and has limited side effects. PDT involves the use of a photo-activated chemotherapeutic agent, benzoporphyrin derivative (verteporfin/Visudyne) given intravenously that when stimulated by non-thermal wavelength-specific light allows for selective ablation of tumor tissue. The light is delivered to the spine through small fiber optic cables (outer diameter 0.98mm, inner core of 0.5mm mm) using a diode laser. Visudyne is an FDA and Health Canada approved photosensitizer that has been used in over one million patients for the treatment of age related macular degeneration, a leading cause of blindness in the elderly. To investigate the use of PDT for spinal metastases the investigators initially developed a bioluminescent metastatic rodent model using human breast cancer that metastasized to the spine. Using this model it was determined that PDT was effective at treating metastatic breast cancer lesions in the spine. The research team next utilized non-tumor bearing canine and porcine models to determine that the treatment could be safely delivered to the spine and conduct light dosimetry analysis. The safety of PDT intra-operatively was assessed using somatosensory evoked potentials and through post-treatment clinical examination and magnetic resonance imaging (MRI). The effects PDT had on the spine were analyzed by comparing pre-operative and post-operative MR imaging and correlating those in turn with histological analysis. None of these animals suffered weakness or complication from the use of PDT around the spinal cord. During these studies the investigators developed the planning, delivery and instrumentation methodologies to deliver PDT to spinal tumors and the methodology to combine this therapy with vertebroplasty, a percutaneous method of stabilizing the spine. In addition, in a separate set of studies, highgrade osteosarcomas in canines were treated to determine the effect PDT had on large bone tumors. The results of this study again provided comparison of pre and post-treatment effects seen on MRI and histological analysis. The volume of effect seen in the osteosarcomas was up to 25cm (cubed) and was comparable to the volume of effect required for complete treatment of spinal lesions. By combining the canine and porcine studies there is strong evidence that PDT is both safe and effective for the treatment of metastatic tumors in the spine.
PDT has many advantages over current therapies; it is targeted, repeatable, minimally invasive and has limited local and systemic side effects. Its use would enhance the treatment options for patients with advanced stage cancer. The goal of the present study is to demonstrate that PDT can be safely and effectively given to treat spinal metastases in patients with advanced stage cancer. The study is a pilot study and will determine the safe and accurate treatment of 30 patients with spinal metastases who have multiple lesions or who have failed radiation or surgical intervention. The effectiveness of this treatment will be determined through clinical and radiographic endpoints with recurrence and survival also determined. The investigators intend to demonstrate that PDT provides a minimally invasive method with low morbidity and mortality by which spinal tumors can be ablated and later stabilized through vertebroplasty, optimizing quality of life and providing effective treatment for this devastating manifestation of advanced stage cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vertebral Metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose escalating PDT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Visudyne
Other Intervention Name(s)
Verteporfin
Primary Outcome Measure Information:
Title
Intraoperative dosimetry
Description
Intraoperative dosimetry data on light transmission and attenuation in patient specific diseased bone will be contrasted to pre-operative imaging data and the region of effect based on actual light transmission compared to pre-operative planning algorithms. These results will gauge the potential accuracy of our planning algorithms.
Time Frame
During surgery
Secondary Outcome Measure Information:
Title
Neurologic function
Description
The primary safety parameter will be unexpected worsening in neurological function.
Physical examination will include a detailed neurological examination (including ASIA score) that assesses the strength, sensation and reflexes of the patient in the upper and lower extremities
Time Frame
7 days, 6 weeks
Other Pre-specified Outcome Measures:
Title
Effect of PDT and vertebral osteoplasty on patient functional outcome - SF36
Description
The analgesic effect of surgical treatment will be estimated using the SF-36
Time Frame
7 days, 6 weeks
Title
Effect of PDT and vertebral osteoplasty on patient functional outcome - VAS scale
Description
The analgesic effect of surgical treatment will be estimated using the visual analogue (VAS) pain scale.
Time Frame
7 days, 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 20 and 85
Established metastatic vertebral bony disease in the spine
Eligible for single level vertebral osteoplasty (i.e. percutaneous vertebroplasty, kyphoplasty)
Patients who are symptomatic with axial pain from vertebral metastatic involvement and are at risk for pathologic fracture; or have had a symptomatic pathologic fracture
Patients who have shown radiographic progression and/or pain symptoms of a documented vertebral metastasis despite non-surgical therapies
Exclusion Criteria:
Progressive neurological compromise
Osteoblastic vertebral metastatic disease
Posterior vertebral cortical/body wall involvement
Spinal canal compromise / neurologic compression
Anticipated life expectancy of less than twelve weeks to live
Cognitive impairment and/or language barriers to study participation
Severe hepatic impairment (Child's C) with active hepatitis or hepatic disease.
Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. CNS metastases must be stable for > 2 weeks prior to screening.)
Nursing mothers, pregnant, currently breastfeeding or trying to get pregnant.
Unable to avoid sun exposure for 5 day post-PDT therapy (per verteporfin precautions).
Hyperphotosensitivity conditions, including porphyria
Hypersensitivity to verteporfin or any other ingredients of Visudyne
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Photodynamic Therapy for the Treatment of Vertebral Metastases
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