Trial Title:
Novel Light Delivery Method for Performing Transbronchial Photodynamic Therapy for Peripheral Lung Cancer
NCT ID:
NCT06262555
Condition:
Lung Cancer
Lung Cancer Metastatic
Conditions: Official terms:
Lung Neoplasms
Conditions: Keywords:
Photodynamic Therapy
Peripheral Lung Cancer
Trans-Bronchoscope Ablation
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Transbronchial PDT peripheral lung tumor ablation
Description:
Transbronchial lung tumor ablation with Photodynamic therapy
Arm group label:
Arm 1
Summary:
This research aims to develop an innovative photodynamic therapy (PDT) for peripheral
lung tumors. Current treatments involve surgery, chemotherapy, and radiation.
Photodynamic therapy, using light and photosensitizing drugs, is promising but has
limitations. Our team proposes using Lipiodol, a contrast agent, instilled into the
trachea via bronchoscopy, surrounding the tumor. Preliminary pig model trials showed
safety. Clinical trials, building on a U.S. study (NCT02916745), commenced in October
2021, treating three cases. Initial results suggest safety, but efficacy requires further
investigation. Based on ongoing trials, we propose a phase I trial with multiple light
treatments from different directions and an additional dose after 48 hours to assess
safety and efficacy. This study will guide future clinical trials for optimal PDT dosage.
Detailed description:
The main focus of this research is the development of an innovative photodynamic therapy
(PDT) mode applied to peripheral lung tumors. Current treatments for lung tumors,
including primary lung cancer or metastatic tumors to the lungs, involve surgery,
chemotherapy (including targeted and immunotherapy), and radiation therapy. The choice of
treatment depends on factors such as tumor size, invasion, genetic characteristics, and
the overall health of the patient.
For early-stage peripheral lung tumors, there is a continuous effort to develop minimally
invasive treatment modalities to replace current surgical methods. Techniques such as
computed tomography-guided percutaneous or bronchoscopic-guided radiofrequency ablation
(RFA), microwave ablation, and photodynamic therapy are actively under research and
development. Photodynamic therapy utilizes special photosensitizing drugs selectively
absorbed by cancer cells, followed by exposure to light of specific wavelengths,
triggering a reaction that destroys cancer cells.
Although photodynamic therapy has been successful in treating early-stage central airway
lung cancer or advanced tumors causing airway obstruction, it has limitations. The
penetration of light is restricted, resulting in a treatment range of approximately 1.5
to 2 centimeters in diameter. Multiple guidance and light treatments are needed to cover
the entire tumor, increasing the technical difficulty of the procedure.
Light travels in a straight line and undergoes penetration, absorption, and reflection
when encountering tissue interfaces, limiting its penetration within tissues. Dr.
Friedberg in the United States proposed a novel lighting mode in 2003, using materials
with high refractive indices, such as mineral oil (refractive index approximately 1.47),
to enable light conduction in the trachea and bronchi. However, mineral oil is harmful to
lung tissue, causing severe complications if inadvertently inhaled into the airways.
In this study, Lipiodol, a contrast agent with a refractive index of 1.47, was considered
as a potential alternative to mineral oil. Lipiodol is a mixture of poppy seed oil and
iodine ions and is commonly used in lymphography or for embolization therapy of liver
tumors. It has been used for years in clinical practice for bronchoscopic instillation as
a means of visualizing and locating lung tumors.
Based on these considerations, the research team hypothesized that by using
electromagnetic navigation bronchoscopy to instill Lipiodol into the proximal trachea of
the lung segment containing the tumor, the tumor could be completely surrounded by
Lipiodol. Subsequent light therapy in the proximal trachea would then illuminate the lung
tissue containing Lipiodol, including the tumor tissue, supplying blood vessels, and
lymphatic tissue, selectively killing tumor tissue and potential early micro-metastases.
The research team conducted preclinical trials using a pig model, confirming that
Lipiodol could be instilled into the peripheral lung tumor location via bronchoscopy.
Moreover, light therapy with the current energy settings (200 J/cm, 400 mW/cm, 500
seconds) in Lipiodol-injected lung tissue was shown to be safe.
A multi-center clinical trial in the United States (ClinicalTrials.gov Identifier:
NCT02916745) explored PDT for peripheral lung tumors. Photofrin was intravenously
injected 48 hours before treatment, and under the guidance of electromagnetic navigation
bronchoscopy and bronchoscopic ultrasound, the light fiber was inserted into the tumor
site for PDT with an energy setting of 200 J/cm, 400 mW/cm, 500 seconds. The trial, as of
January 2019, included five patients with no reports of severe complications, indicating
initial safety and feasibility. Building upon this trial and the team's proposed novel
PDT lighting mode, a phase I human clinical trial was initiated in October 2021 and is
ongoing until February 2022. Three cases have been treated, and the initial observations
suggest safety and feasibility. One patient, unfortunately, succumbed to obstructive
pneumonia six weeks after treatment due to rapid disease progression, but it was not
considered a treatment-related complication.
Although the effectiveness of the treatment was not as anticipated, further clinical
trials are needed to determine the optimal lighting dosage. In the ongoing trial
(NCT02916745), two cases received multiple light treatments from different directions
without significant complications. A case report by Dr. Allison demonstrated successful
and complication-free bronchoscopic PDT with two light treatments 48 hours apart in a
patient ineligible for standard treatments.
The next phase of clinical trials is proposed based on the team's 2022 single-light
treatment trial, aiming to assess safety and efficacy using multiple light treatments in
different directions and an additional dose 48 hours later. This study will serve as a
reference for the minimum basic lighting dosage (NOAEL) and the possible effective dosage
for future phase I clinical trials.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients diagnosed with advanced or terminal malignant lung tumors (including
primary lung cancer and lung metastases from other cancers).
- Patients who have failed standard treatments (surgery, radiotherapy, or first and
second-line chemotherapy/immunotherapy/targeted therapy) or are unsuitable for
standard treatments.
- Tumor size less than or equal to 3 cm, clearly assessable on chest computed
tomography.
Patients capable of providing informed consent and willing to undergo regular follow-ups
during the trial.
Exclusion Criteria:
- Diagnosis of small cell lung cancer or non-solid malignancies.
- Tumors located in the central part of the lungs.
- Previous radiation therapy to the treatment site.
- Abnormal blood biochemical values.
- Chemotherapy received within the past 4 weeks.
- Tumor invading major blood vessels.
- Allergy to porphyrins or porphyrin-related metabolites, or allergy to Lipiodol or
iodine-containing contrast agents.
- Planning radical surgery for lung tumors within the next 90 days.
- Potential need for slit lamp ophthalmic examination within the next 30 days due to
existing eye diseases.
- Inability to undergo bronchoscopy due to mental health conditions.
- Pregnancy, planning pregnancy, breastfeeding, or planning to breastfeed within the
next 6 months.
- Previous photodynamic therapy within the past 1 month.
- Severe kidney or liver disease with abnormal function.
- Planning to participate in other cancer treatment clinical trials within the next 3
months.
- HIV-positive patients.
- Individuals deemed unsuitable for the trial by the principal investigator and the
safety monitoring committee due to severe illnesses.
Gender:
All
Minimum age:
20 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Taoyuan General Hospital, Ministry of Health and Welfare
Address:
City:
Taoyuan City
Zip:
320
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Yei-San Hsieh, MD
Phone:
+886-975061108
Email:
yeisanh@gmail.com
Investigator:
Last name:
Yei-San Hsieh, Dr.
Email:
Principal Investigator
Investigator:
Last name:
Hwi-Lu Chang, Dr.
Email:
Sub-Investigator
Start date:
March 2024
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Taoyuan General Hospital
Agency class:
Other
Source:
Taoyuan General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06262555
