Padeliporfin VTP Using Robotic Assisted Bronchoscopy in Peripheral Lung Cancer

Study Overview
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Brief Summary
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Phase 1/1b, safety, feasibility, and light dose titration study followed by further study of therapeutic ablation effects. Patients with high risk of peripheral primary lung cancer, stage 1A1/1A2, for whom surgical treatment is planned, will be recruited. Surgery will be performed at 5-21 days following the VTP procedure. Study intervention: robotic assisted bronchoscopic Padeliporfin VTP lung ablation: vascular targeted photodynamic therapy using Padeliporfin photosensitizer.

Detailed Description
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A multicenter, open label, phase 1/1b, safety, feasibility, and light dose titration study followed by further study of therapeutic ablation effects. Patients with high risk of peripheral primary lung cancer, stage 1A1/1A2, for whom surgical treatment is planned, will be recruited. Patients who are candidates for lung resection will be recruited as a diagnose and treat in the same anaesthesia, protocol; surgery will be performed at least 5 days and up to 21 days following the VTP procedure. Study intervention will consist of robotic assisted bronchoscopic Padeliporfin VTP lung ablation: vascular targeted photodynamic therapy using Padeliporfin photosensitizer, an ablation mechanism with efficacy related to immune response post-ablation.

Official Title
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A Multicenter Open-label Phase 1/1b Study to Evaluate Safety, Feasibility and Early Treatment Effect of Padeliporfin VTP Using Robotic Assisted Bronchoscopy and Cone Beam CT Guidance in Patients With Peripheral Lung Cancer

Conditions
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Peripheral Lung Tumor

Intervention / Treatment
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* Combination Product: Padeliporfin Vascular Targeted Photodynamic (VTP) therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 Patients with primary lung lesions who are at high risk for primary lung cancer. 2.1.Biopsy with intraoperative confirmation of malignancy using on-site cytology will be used as final inclusion prior to study treatment. All patients will be approved by a multi-disciplinary team (thoracic surgery, interventional pulmonology, medical oncology and radiation oncology) as appropriate for bronchoscopic VTP prior to surgical resection. Tumor size targeted for VTP treatment ≤ 2 cm (Part A) and <3cm (Part B), based on CT scan, including solid or semi-solid tumors. EBUS mediastinal staging performed intraoperative prior to VTP treatment with rapid on-site evaluation negative for nodal involvement of malignancy. Tumor is ≥ 2cm from the central bronchial tree (distal 2 cm of the trachea, carina, and named major lobar bronchi up to their first bifurcation) (Timmerman, 2018). Lung lesion is not contiguous with and ≥ 1 cm from the pleura/fissures. Patient is eligible to undergo bronchoscopy under general anesthesia. Tumor is accessible for Padeliporfin VTP treatment via robotic bronchoscopy ECOG performance score 0-2 Estimated life expectancy of ≥3 months Adequate organ system function Negative serum pregnancy test Exclusion Criteria: Patient has a centrally located lung lesion, as defined by RTOG within 2 cm of the proximal bronchial tree, or within 2 cm of other major mediastinal structure (aorta, heart, trachea, pericardium, superior vena cava, pulmonary artery, esophagus, vertebra's body or spinal canal). Patient has a lung lesion located less than 1 cm from the pleura or fissure Patient has a lung cancer lesion >2cm in diameter, for the expansion cohort lesion >2-3 cm Patient has cytologic or histologic evidence of nodal disease Tumor invades major vessels Prior exposure to VTP or PDT treatments Pregnant or breastfeeding women Receiving any other investigational treatment Co-morbidities: Baseline hypoxia with O2 saturation <92% on 2L NC or more of oxygen New York Heart Association (NYHA) stage III/IV heart failure Unstable coronary artery disease or MI within the last 6 months Uncontrollable clinically serious arrhythmia Decompensated/clinically worsening interstitial lung disease or obstructive lung disease. Unstable cerebrovascular or peripheral vascular disease Inability to stop anticoagulation or anti-platelet therapy peri-procedure Evidence of clinically active infection requiring systemic (any route) antibiotic therapy. All prior infections must have resolved following optimal therapy. Patient has any acute or chronic condition assessed as clinically significant by Investigator which may preclude bronchoscopy procedure History of medical or psychiatric disease which, in the view of the investigator, would preclude safe treatment or acceptable study compliance Known severe pulmonary hypertension (mean pulmonary arterial pressure ≥ 50 mmHg) Patient has a cancer diagnosis with active disease requiring further cancer therapy. Patient has had major surgery within the last 4 weeks. Patient has porphyria or hypersensitivity to padeliporfin or porphyrin-like compounds or to any of its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part B recruitment will be opened upon completion of Part A light dose escalation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>will be a monotherapy light dose escalation with single dose of Padeliporfin at light laser doses of 150, 250 and 400 mW/cm for 20 minutes. Part A will proceed with light dose escalation and will continue until the maximum tolerated light dose (MTD) and/or recommended phase 2 dose (RP2D) is defined. | Combination Product: Padeliporfin Vascular Targeted Photodynamic (VTP) therapy<br>* Bronchoscopy will be performed with robotic assisted approach using standard practices using general anaesthesia and placement of the optic fiber intratumorally followed by IV administration of Padeliporfin for 10 min and laser light illumination.<br>* Other names: Padeliporfin VTP;|
| Experimental: Part B<br>will be a dose expansion part at MTD/RP2D dose level identified in Part A to further assess the safety, tolerability, and treatment effect of the MTD and/ or RP2D | Combination Product: Padeliporfin Vascular Targeted Photodynamic (VTP) therapy<br>* Bronchoscopy will be performed with robotic assisted approach using standard practices using general anaesthesia and placement of the optic fiber intratumorally followed by IV administration of Padeliporfin for 10 min and laser light illumination.<br>* Other names: Padeliporfin VTP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of robotic assisted bronchoscopic Padeliporfin VTP ablation | Incidence of treatment-related adverse events as assessed by CTCAE v5.0 | Day 30 | 
| Feasibility of robotic assisted bronchoscopic Padeliporfin VTP treatment | Feasibility of robotic bronchoscopic light fiber delivery into the target lesion as confirmed by cone beam CT and complete VTP treatment | Day 1 | 
| Evaluate Maximum Tolerated light Dose and/or RP2D of Padeliporfin VTP ablation | Evaluate Maximum Tolerated light Dose and/or RP2D of robotic assisted bronchoscopic Padeliporfin VTP ablation (a vascular targeted photodynamic therapy with Padeliporfin of patients with peripheral stage 1A1/1A2) primary non-small cell lung cancers. | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation lung surgery feasibility | Number and severity of operative, postoperative adverse events Number and length of any delays to surgery or surgical cancellations Number of completed surgeries | Day 5-21 | 
| Evaluation of the ablation area | Acute radiographic changes on CT chest imaging obtained two days post Padeliporin VTP treatment | 2 days post Padeliprofin VTP |