An Open-Labeled, Single Arm Phase 2 Efficacy and Safety Study of REM-001 Photodynamic Therapy (PDT) for Treatment of Cutaneous Metastatic Breast Cancer (CMBC)

摘要 皮肤转移性乳腺癌(CMBC)在高达24%的转移性乳腺癌患者中发生。 在这种情况下，全身治疗的效果往往有限，手术和放射治疗只能提供短暂的缓解。 由于涉及的副作用和皮肤损伤的程度，它们在CMBC人群中的使用可能会受到限制 损伤。CMBC可引起感染、出血、异味和毁容，并可进展到占据大片区域 在身体上。金塔拉提出了一种名为REM-001疗法的光动力疗法(PDT)，其中 光敏药物被注射到体内，在肿瘤部位收集，并由专门设计的 激光聚焦在选定的病变上。这种活性药物可以在对周围环境影响最小的情况下摧毁肿瘤 组织。REM-001已被证明在许多情况下都有效，包括CMBC。然而，之前的试验 使用高于阈值的剂量也报告了较高的不良副作用发生率和较长的愈合时间。在……里面 在以前的试验中，焦痂和溃疡等症状会增加恢复时间，并导致患者离开 研究，但与更好的病变结果无关。该项目将把治疗剂量减少到 之前确定的阈值水平-在最初的研究中显示了79%的应答率-在一项努力中 以减少副作用，同时仍在治疗皮损。金塔拉将在15名患者身上测试减少的剂量 不能接受手术或放射治疗的症状性皮肤损害和稳定的全身疾病 在治疗的时候。这些患者将接受单次剂量的REM-001，然后进行光线治疗 并将监测疗效(病变缩小或消失，以及疼痛和瘙痒消退) 改善生活质量)和安全性/耐受性(焦痂和溃疡，以及出血和排出 治疗相关的光敏性，以及标准的临床副作用监测)。患者会 继续他们现有的护理标准系统治疗，并将在整个试验期间接受治疗。如果这场审判是 成功--随着治疗剂量的减少，治疗的皮损缩小或消失--金塔拉将继续 CMBC的多部位III期试验和探索REM-001光动力疗法在其他皮肤中的应用 有迹象表明。

ABSTRACT Cutaneous metastatic breast cancer (CMBC) develops in up to 24% of patients with metastatic breast cancer. Systemic therapy often has limited efficacy in such cases, and surgery and radiotherapy offer only transient relief and their use may be limited in the CMBC population due to the side-effects involved and the extent of cutaneous lesions. CMBC can cause infection, bleeding, malodor and disfigurement and can progress to occupy large areas of the body. Kintara proposes a photodynamic therapy (PDT) known as REM-001 Therapy, wherein a photosensitive drug is injected into the body to collect at tumor sites, and is activated by a specially-designed laser focused on the selected lesions. The activated drug destroys tumors with minimal effects to surrounding tissue. REM-001 has been proven to be effective for many conditions, including CMBC. However, previous trials using a higher-than-threshold dose also reported high rates of unwanted side effects and longer healing time. In previous trials, symptoms such as eschar and ulceration increased recovery time and caused patients to leave studies but was not associated with better lesion outcomes. This project will reduce the treatment dosage to the previously identified threshold level – which demonstrated a 79% response rate in an initial study – in an effort to reduce side effects while still treating lesions. Kintara will test the reduced dose on 15 patients with symptomatic cutaneous lesions and stable systemic disease who are unable to receive surgery or radiotherapy at the time of treatment. These patients will be administered a single dose of REM-001 followed by light treatment and will be monitored for efficacy (lesion shrinking or disappearing, as well as pain and itch subsiding and improved quality of life) and safety/tolerability (eschar and ulceration, and bleeding and discharge from the lesions, treatment related photosensitivity, as well as standard clinical side-effect monitoring). Patients will continue on their existing standard of care systemic therapy and will receive it throughout the trial. If this trial is successful – the treated lesions shrink or disappear with the reduced treatment dose – Kintara will continue to a multi-site Phase III trial for CMBC and explore the use of REM-001 photodynamic therapy in other dermal indications.