Feasibility Study of Using Navigational Bronchoscopy to Perform PDT-Photofrin® in Unresectable Peripheral Lung Cancer

Multicenter, Prospective, OL, Single-arm Clinical Study of Safety & Feasibility of Using Navigational Bronchoscopy to Perform Interstitial PD Therapy Using Photofrin® as Treatment in Subjects With Unresectable Solid Tumor in Peripheral Lung

This research study is being conducted to assess the safety and feasibility of using a new developed bronchoscopic technology called electronavigational bronchoscopy to treat subjects with solid tumor in peripheral lung, who are inoperable or refused surgery. It will involve 10 sites in USA and Canada. Participation will last 6 months.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer (NSCLC); Lung Metastasis
• Intervention / Treatment: Drug: Porfimer sodium; Device: Fiber optic

Detailed Description

Lung cancer accounts for almost one-third of cancer deaths. Cancer screening strategies have the potential to achieve a 20% reduction in death rates. Newly developed bronchoscopic technologies (such as navigational bronchoscopy) have shown to enable physicians to safely reach lesions in peripheral regions of the lung and obtain diagnosis. This new technology may now potentially offer bronchoscopic therapeutic interventions, such as photodynamic therapy, to tumors that were previously unreachable due to their peripheral anatomic location.

Photodynamic therapy (PDT) uses a combination of a photosensitizing drug (a drug that is activated by light), called porfimer sodium (Photofrin®), and a light from a laser that emits no heat. This technique works to allow the medical doctor to specifically target and destroy abnormal or cancer cells while limiting damage to surrounding healthy tissue. The activation of the drug is done by lighting the abnormal area using a fiber optic device (very fine fiber [like a fishing line] that permits light transmission) inserted into a flexible tube called bronchoscope. The light activates the porfimer sodium, which is concentrated in the abnormal tissue, leading to its destruction.

The purpose of this study is to determine if physicians can reach the tumors in the periphery of the lung via electronavigational bronchoscopy and deliver the photodynamic therapy by placing the optical fiber into the tumor.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • Toronto General Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30265
      • Southeastern Regional Medical Center
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Hospital Network
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Southwestern Regional Medical Center
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged 18 or older
• Diagnosed with histologically confirmed solid tumor located in the peripheral lung
• Not candidate for curative surgery, is unfit for surgery, or does not wish to undergo curative surgery
• May be candidate for, have failed, or does not wish to undergo radiation therapy
• The tumor is ≤ 3 cm in size and clearly observable in computerized tomography (CT scan)
• Able to sign an informed consent

Exclusion Criteria:

• Diagnostic of small cell lung cancer
• Solid tumor located in central lung
• Presence of concurrent non-solid malignancy
• Abnormal blood results
• Received chemotherapy/immunotherapy in the last 4 weeks
• Tumor invades a major blood vessel
• Porphyria or known hypersensitivity to Photofrin® or porphyrin-like compounds or to any of its excipients
• Planned surgical procedure within the next 90 days
• Coexisting ophthalmic disease likely to require slit-lamp examination within the next 90 days
• Acute or chronic medical or psychological illnesses that prevent endoscopy procedures
• Pregnant or intend to become pregnant, breastfeeding or intend to breastfeed during the study
• Received PDT during the past 3 months
• Severe impairment of your kidney or liver function
• Participates or intends to participate in another drug study (other than observational studies) during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Photodynamic therapy-Photofrin; Photodynamic therapy (PDT) involves the i.v. injection of 2 mg/kg-porfimer sodium (Photofrin®) followed by illumination of the tumor using a fiber optic device during navigational bronchoscopy. Two days after the injection, a laser light will be applied to the tumor.

Drug: Porfimer sodium; After injection of porfimer sodium (Photofrin®), a flexible bronchoscopy with navigation guidance will be performed to confirm the location and the size of the lesion with the use of radial probe endobronchial ultrasonography (REBUS). A light dose of 200 J/cm of diffuser length will be delivered.; Other Names: Photofrin; Device: Fiber optic; A fiber optic diffuser length matching the tumor length will be placed in the lesion under fluoroscopy guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility to Perform Interstitial-Photodynamic Therapy (i-PDT) Into Tumor	Number of times photodynamic therapy was delivered into the tumor using navigational bronchoscopy for each subject.	Day 3 post-treatment
Adverse Events Incidence Indicating Safety of Navigational Bronchoscopy-interstitial-Photodynamic Therapy (i-PDT)	The incidence of adverse events following navigational bronchoscopy-iPDT (interstitial-Photodynamic Therapy) will be presented as the primary safety indicator for this treatment.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response at 3 Months Post Photodynamic Therapy (PDT)	From the start of treatment until 3 months post-treatment measured as per the Modified RECIST (Response Evaluation Criteria in Solid Tumors) Criteria	Up to 3 months
Tumor Response at Study Exit (6 Months) Post Photodynamic Therapy (PDT)	From the start of treatment until 6 months post-treatment measured as per the Modified RECIST (Response Evaluation Criteria in Solid Tumors) Criteria	Up to 6 months
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at Screening (Days -14 to -1). Baseline.	Measured at screening to be the baseline measure. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	up to day 0 (-14 to -1 days)
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at Day 1 (Date of Photofrin Injection).	Measured at Day 1 which is day of the photofrin injection. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	1 day
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at Day 3 (Day of Photodynamic Therapy)	Measured at Day 3. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	Day 3
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at Day 30 (30 Days Post Photofrin Injection)	Measured at Day 3. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	Day 30
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at 3 Months Post Photofrin Injection	Measured at 3 months. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	up to 3 months
Performance Status on the Eastern Cooperative Oncology Group (ECOG) Score at 6 Months Post Photofrin Injection	Measured at 6 months. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.	Up to 6 months
Short Form Health Survey (SF-36) Score at Baseline	The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.	Baseline
Short-Form Health Survey (SF-36) Score at Follow-up Visit at 3 Months.	The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.	up to 3 months
Short-Form Health Survey (SF-36) Score at Study Exit (6 Month Visit)	The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.	Up to 6 months
Health-related Quality of Life on the 4- and 7-point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 Item (QLQ-C30): Baseline	Baseline score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.	Baseline
Health-related Quality of Life on the 4- and 7-point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 Item (QLQ-C30): Follow-up 3 Months	3 month score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.	up to 3 months
Health-related Quality of Life on the 4- and 7-point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30 Item (QLQ-C30): 6 Months	6 month score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.	Up to 6 months
Health-related Quality of Life on the 4- Point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Lung Cancer 13 Item (QLQ-LC13): Baseline Score	Baseline measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.	Baseline
Health-related Quality of Life on the 4- Point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Lung Cancer 13 Item (QLQ-LC13): Follow-up 3 Month Score	3-Month measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.	up to 3 months
Health-related Quality of Life on the 4- Point European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Lung Cancer 13 Item (QLQ-LC13): Study Exit (6 Months) Score	6-Month measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.	Up to 6 months
Number of Participants With Indicated Adverse Events	Adverse events (AEs) noted by number of participants with at least one event. An AE was defined as any untoward medical occurrence in a subject during the course of the study, regardless of causal relationship. AEs were coded using MedDRA Version 21.1	Up to 6 months post-treatment
Number of Subjects With at Least One Serious Adverse Event	The number of subjects with at least one serious adverse event are listed.	Up to 6 months
Safety: Physical Examination Summaries for Each Subject	Safety evaluation will include the physical examinations summary of non-normal findings for each subject.	Up to 6 months
Safety: Number of Participants With Indicated Vital Sign Summaries	Safety evaluation included vital sign summary for each subject. Vital signs included pulse, blood pressure, temperature and respiration rate. Only clinically relevant results, as per the investigator judgement, are included. These would be vital signs that are out of the normal range but could be considered outside enough to be clinically relevant to the subject's health.	Up to 6 months
Safety: Number of Participants With Indicated Changes to Pulmonary Function Tests (PFTs) Related to Treatment Emergent Adverse Events	The treatment emergent adverse events related to PFTs are noted. Pulmonary function test measurements were: Diffusion Capacity of Lung for Carbon Monoxide (%), Expiratory Reserve Volume (mL), Forced Vital Capacity (mL), Forced Expiratory Volume in 1 second (mL), Forced Expiratory Flow 25% to 75% (L/min), Functional Residual Capacity (mL), Maximum Voluntary Ventilation (L/min), Residual Volume (mL), Peak Expiratory Flow (L/min), Slow Vital Capacity (mL), Total Lung Capacity (mL)	Up to 6 months
Safety: Laboratory Test Summaries for Each Subject	Safety evaluation includes laboratory tests summarized for each subject with any abnormal lab results considered an Adverse Event to be listed. The investigators commented on any laboratory value outside the normal reference range. If the value was judged to be an Adverse Event, it is listed. The values analysed were: Hematology (Hemoglobin, Hematocrit, White Blood Cell, Red Blood Cell, Platelet Count, Prothrombin Time) and Chemistry (Glucose (random), Blood Urea Nitrogen, Electrolytes (sodium, potassium, chloride), Creatinine, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, Total Bilirubin, Albumin, Total Protein)	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunology Markers Concentrations Were Examined as an Exploratory Endpoint. The Change From Baseline Was Reported.	Distribution of lymphocyte subsets from peripheral blood was determined by flow cytometry. Flow cytometry is a laser-based technique used to detect and measure physical and chemical characteristics of a population of cells or particles. It allows simultaneous multi-parameter analysis of single cells. The selected markers of interest, representative of the broader markers were: Total Thymus-cells (T-Cells), Cluster of Differentiation 4 (CD4) T cell subsets, and Cluster of Differentiation 9 (CD8) T cell subset, CD4 T Regulatory (T Reg) cells, Natural Killer Cells, Activated T cells, Myeloid-Derived Suppressor Cells (MSCDs), Monocytes. The Percent Gated and Absolute counts were analysed for each marker. Gating allows the analysis to be restricted to a specific size of cells (e.g. lymphocytes) to allow a more specific analysis. Absolute counting quantifies the total number of cells. It is recommended to look at both values to get the full picture.	Baseline, 10 days post-treatment
Skin Photosensitivity as a Adverse Event of Special Interest: Participants With Event	Adverse Event of special interest was Skin Photosensitivity. Skin photosensitivity was examined because all subjects who receive Photofrin are photosensitive and must observe precautions to avoid exposure of eyes and skin to direct sunlight or bright indoor lights for 30 days or longer. Changes in skin will be assessed by grade of erythema, edema and blistering and will be tabulated by Common Terminology Criteria for Adverse Events (CTCAE) grade in the dermatology/skin category.	Up to 6 months

Collaborators and Investigators

• Sponsor: Concordia Laboratories Inc.
• Investigators: Study Director: Michelle Depot, Ph.D., at the request of Concordia Laboratories Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 26, 2017
• Primary Completion (ACTUAL): April 12, 2019
• Study Completion (ACTUAL): April 12, 2019

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (ESTIMATE): September 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 4, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: NSCLC; lung cancer; Non-small cell lung cancer; lung metastasis; lung carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Dihematoporphyrin Ether; Trioxsalen
• Other Study ID Numbers: CLI-PHO1601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No