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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Feasibility of robotic assisted bronchoscopic Padeliporfin VTP treatment
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Part A
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.
干预措施: Padeliporfin Vascular Targeted Photodynamic (VTP) therapy (Combination Product)
Part B
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
干预措施: Padeliporfin Vascular Targeted Photodynamic (VTP) therapy (Combination Product)
结局指标
主要结局
Feasibility of robotic assisted bronchoscopic Padeliporfin VTP treatment
时间窗: Day 1
Feasibility of robotic bronchoscopic light fiber delivery into the target lesion as confirmed by cone beam CT and complete VTP treatment
Evaluate Maximum Tolerated light Dose and/or RP2D of Padeliporfin VTP ablation
时间窗: Day 14
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.
Safety of robotic assisted bronchoscopic Padeliporfin VTP ablation
时间窗: Day 30
Incidence of treatment-related adverse events as assessed by CTCAE v5.0
次要结局
- Evaluation of the ablation area(2 days post Padeliprofin VTP)
- Evaluation lung surgery feasibility(Day 5-21)